Highly crystalline cross-linked oxidation-resistant polyethylene

ABSTRACT

The present invention relates to methods for making highly crystalline cross-linked polymeric material, for example, highly crystalline cross-linked ultra-high molecular weight polyethylene (UHMWPE). The invention also provides methods of making antioxidant-doped highly crystalline cross-linked polymeric material using high pressure and high temperature crystallization processes, medical implants made thereof, and materials used therein.

This application is a national stage of PCT/US2005/003305 filed Feb. 3,2005, which claims priority to Provisional Application No. 60/541,073filed Feb. 3, 2004. The entirety of which are hereby incorporated byreference.

FIELD OF THE INVENTION

The present invention relates to methods for making crystallineoxidation-resistant cross-linked polymeric materials, including highlycrystalline oxidation-resistant cross-linked polymeric materials.Methods of crystallizing cross-linked polymeric materials under highpressure at elevated temperature and materials used therewith also areprovided.

BACKGROUND OF THE INVENTION

Total joint arthroplasty for end-stage joint diseases most commonlyinvolves a metal/polymer articular pair. Polyethylene, particularlyultrahigh molecular weight polyethylene (UHMWPE), has been and remainsthe material of choice for the load-bearing, articulating surface forthis articular pair for more than four decades (Kurtz, et al.,Biomaterials, 1999. 20(18): p. 1659-1688). Despite high long-termsuccess rates for such reconstructions, wear and fatigue damage ofpolyethylene limit the longevity of total joints. In total knees,implant failure is caused primarily by fatigue damage to thepolyethylene components (Collier, et al., J. Arthroplasty, 1996. 11(4):p. 377-389). One solution to prevent osteolysis in total hips iscross-linking, which markedly reduces polyethylene wear (Muratoglu, etal., J Arthroplasty, 2001. 16(2): p. 149-160; Muratoglu, et al.,Biomaterials, 1999. 20(16): p. 1463-1470; McKellop, et al., J OrthopRes, 1999. 17(2): p. 157-167).

Increased crosslink density in polymeric material is desired in bearingsurface applications for joint arthroplasty because it significantlyincreases wear resistance. Oxidation-resistant cross-linked polymericmaterial, such as UHMWPE, is desired in medical devices because itsignificantly increases the wear resistance of the devices. A method ofcross-linking is by exposing the UHMWPE to ionizing radiation. However,cross-linking also reduces the fatigue strength of polyethylene,therefore limiting the use of highly cross-linked polyethylenes in totalknees where the components are subjected to cyclic loading accompaniedby high stresses. Ionizing radiation, in addition to cross-linking, alsowill generate residual free radicals, which are the precursors ofoxidation-induced embrittlement. This is known to adversely affect invivo device performance. Therefore, it is desirable to reduce theconcentration of residual free radicals, preferably to undetectablelevels, following irradiation to avoid long-term oxidation.

One way of substantially reducing the concentration of residual freeradicals in irradiated UHMWPE is to heat the irradiated UHMWPE to aboveits melting temperature (for example, about 137° C.-140° C.). Meltingfrees or eliminates the crystalline structure, where the residual freeradicals are believed to be trapped. This increase in the free radicalmobility facilitates the recombination reactions, through which theresidual free radical concentration can be markedly reduced. Thistechnique, while effective at recombining the residual free radicals,has been shown to decrease the final crystallinity of the material. Thisloss of crystallinity will reduce the modulus of the UHMWPE. Yet forhigh stress applications, such as unicompartmental knee designs, thinpolyethylene tibial knee inserts, low conformity articulations, etc.,high modulus is desired to minimize creep.

Cross-linking by irradiation decreases the fatigue strength of UHMWPE.In addition, post-irradiation melting further decreases the fatiguestrength of the UHMWPE. Radiation and melting also decrease the yieldstrength, ultimate tensile strength, toughness and elongation at breakof UHMWPE.

Melting in combination with irradiation creates cross-links andfacilitates recombination of the residual free radicals trapped mostlyin the crystalline regions, which otherwise would cause oxidativeembrittlement upon reactions with oxygen. Both cross-linking andmelting, however, decrease the crystallinity of UHMWPE. Cross-linkingand decrease in the crystallinity is thought to be the reason fordecrease in fatigue strength, yield strength, ultimate tensile strength,toughness and elongation at break. Some or all of these changes inproperties limit the use of low wear highly cross-linked UHMWPE to lowstress applications. Therefore, a cross-linked UHMWPE with highercrystallinity is desirable for low wear and high fatigue resistance forhigh stress application that require low wear.

It is, therefore, desirable to reduce the irradiation-created residualfree radical concentration in cross-linked UHMWPE without reducingcrystallinity, so as to achieve high fatigue resistance for high stressapplication that require low wear. Alternative methods to melting can beused to prevent the long-term oxidation of irradiated UHMWPE to preservehigher levels of crystallinity and fatigue strength.

The effect of crystallinity on the fatigue strength of conventionalUHMWPE is known. Investigators increased the crystallinity ofunirradiated UHMWPE by high-pressure crystallization, which increasedthe fatigue crack propagation resistance of unirradiated UHMWPE by about25% (Baker et al., Polymer, 2000. 41(2): p. 795-808). Others found thatunder high pressures (2,000-7,000 bars) and high temperatures (>200°C.), polyethylene grows extended chain crystals and achieves a highercrystallinity level (Wunderlich et al., Journal of Polymer Science PartA-2: Polymer Physics, 1969. 7(12): p. 2043-2050). However, high-pressurecrystallization of highly cross-linked UHMWPE has not been previouslyattempted or discussed. Also, the crystallization behavior of highlycross-linked polyethylene at high pressures has not been determined.

Polyethylene undergoes a phase transformation at elevated temperaturesand pressures from the orthorhombic to the hexagonal crystalline phase.The hexagonal phase can grow extended chain crystals and result inhigher crystallinity in polyethylene. This is believed to be aconsequence of less hindered crystallization kinetics in the hexagonalphase compared with the orthorhombic phase. One could further reduce thehindrance on the crystallization kinetics by introducing a plasticizingor a nucleating agent into the polyethylene prior to high-pressurecrystallization. The polyethylene can be doped with a plasticizingagent, for example, α-tocopherol or vitamin E, prior to high-pressurecrystallization. The doping can be achieved either by blending thepolyethylene resin powder with the plasticizing agent and consolidatingthe blend or by diffusing the plasticizing agent into the consolidatedpolyethylene. Various processes of doping can be employed as describedin U.S. application Ser. No. 10/757,551, filed Jan. 15, 2004, andPCT/US/04/00857, filed Jan. 15, 2004, the entirety of which are herebyincorporated by reference.

SUMMARY OF THE INVENTION

The present invention relates generally to methods of making crystallineoxidation-resistant cross-linked polymeric material, preferably thecross-linked material has higher crystallinity than obtainable withprevious methodologies. More specifically, the invention relates tomethods of radiation cross-linking highly crystalline UHMWPE andsubsequently treating the UHMWPE to increase its oxidation resistance.Also the invention relates to methods of crystallizing cross-linkedultra-high molecular weight polyethylene (UHMWPE) under high pressure atelevated temperature in the hexagonal phase, whereby extended chaincrystals are present and high crystallinity are achieved, followed bytreating the UHMWPE to increase its oxidation resistance. The inventionalso relates to methods of crystallizing cross-linked ultra-highmolecular weight polyethylene (UHMWPE) under high pressure at elevatedtemperature in the hexagonal phase where high crystallinity is achievedand the residual free radical population is reduced. Also the inventionrelates to methods of increasing the crystallinity ofoxidation-resistant crosslinked UHMWPE containing no detectable residualfree radicals or with a reduced free radical population by high-pressurecrystallization.

The process comprises steps of crystallizing polyethylene under highpressure at elevated temperature, irradiating at different temperaturesbelow the melt to control the amount of amorphous, folded and extendedchain crystals during cross-linking. This invention also relates toprocesses to increase oxidation resistance where an antioxidant isincorporated into polyethylene, or a cross-linked polyethylene ismechanically deformed and annealed, or a high pressure and hightemperatures are applied to the cross-linked polyethylene. The processescan be used separately or together in various orders in accordance withthe teachings herein and the skill in the art. All ranges set forthherein in the summary and description of the invention include allnumbers or values thereabout or therebetween of the numbers of therange. The ranges of the invention expressly denominate and set forthall integers and fractional values in the range.

One aspect of the invention provides methods of making highlycrystalline cross-linked polymeric material comprising: a) heating apolymeric material to a temperature above the melt; b) pressurizing theheated polymeric material, preferably under a pressure of at least about10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; c) holding at this pressure; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto about an atmospheric pressure level, thereby forming a highlycrystalline polymeric material; and f) irradiating the highlycrystalline polymeric material at a temperature below the melt withionizing radiation, thereby forming a highly crystalline cross-linkedpolymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked polymeric material comprising: a)heating a polymeric material to a temperature above the melt; b)pressurizing the heated polymeric material under at least about 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; c) holding at this pressure; d) cooling the heated polymericmaterial to about room temperature; e) releasing the pressure to aboutan atmospheric pressure level, thereby forming a highly crystallinepolymeric material; f) irradiating the highly crystalline polymericmaterial at temperature below the melt with ionizing radiation, therebyforming a highly crystalline cross-linked polymeric material; g) heatingthe highly crystalline cross-linked polymeric material to a temperatureabove the melt; h) pressurizing the heated polymeric material under atleast about 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa, i) holding at this pressure; j)cooling the heated polymeric material to about room temperature; and k)releasing the pressure to about an atmospheric pressure level, therebyforming oxidation-resistant cross-linked polymeric material.

In another aspect, invention provides methods of making highlycrystalline cross-linked polymeric material comprising: a) pressurizinga polymeric material under at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa; b) heatingthe pressurized polymeric material to a temperature above 100° C. tobelow the melt of the pressurized polymeric material; c) holding at thispressure; d) cooling the heated polymeric material to about roomtemperature; e) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline polymeric material; and f)irradiating the highly crystalline polymeric material at a temperaturebelow the melt with ionizing radiation, thereby forming a highlycrystalline cross-linked polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked polymeric material comprising: a)pressurizing a polymeric material under at least about 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; b) heating the pressurized polymeric material to a temperaturebelow the melt of the pressurized polymeric material, such as below 140°C.; c) holding at this pressure; d) cooling the heated polymericmaterial to about room temperature; e) releasing the pressure to aboutan atmospheric pressure level, thereby forming a highly crystallinepolymeric material; f) irradiating the highly crystalline polymericmaterial at temperature below the melt with ionizing radiation, therebyforming a highly crystalline cross-linked polymeric material; g) heatingthe highly crystalline cross-linked polymeric material to a temperatureabove the melt; h) pressurizing the heated polymeric material under atleast about 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa; i) holding at this pressure; j)cooling the heated polymeric material to about room temperature; and k)releasing the pressure to about an atmospheric pressure level, therebyforming oxidation-resistant cross-linked polymeric material.

In another aspect, the oxidation-resistant highly crystallinecross-linked polymeric material is machined, thereby forming a medicalimplant. In another aspect, the oxidation-resistant highly crystallinecross-linked medical implant is packaged and sterilized by ionizingradiation or gas sterilization, thereby forming a sterileoxidation-resistant highly crystalline cross-linked medical implant.

In one aspect, the invention provides methods of making a cross-linkedhighly crystalline blend of polymer and additive comprising: a) blendingpolymeric material with an additive; b) consolidating the blend; c)pressurizing the blend under at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa; d) heatingthe pressurized the blend to a temperature of above 100° C. to below themelt of the pressurized blend; e) holding at this pressure; f) coolingthe heated the blend to about room temperature; g) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material; and h) irradiating the highlycrystalline polymeric material at temperature below the melt withionizing radiation, thereby forming a highly crystalline cross-linkedblend of polymer and additive.

In one aspect, the invention provides methods of making a cross-linkedhighly crystalline blend of polymer and additive comprising: a) blendingpolymeric material with an additive; b) consolidating the blend; c)heating the blend to a temperature above the melting point of the blend;d) pressurizing the blend under at least about 10-1000 MPa, preferablyat least about 150 MPa, more preferably at least about 250 MPa; e)holding at this pressure; f) cooling the heated the blend to about roomtemperature; g) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline polymeric material; and h)irradiating the highly crystalline polymeric material at temperaturebelow the melt with ionizing radiation, thereby formingoxidation-resistant highly crystalline cross-linked blend of polymer andadditive.

In one aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymer andadditive comprising: a) blending polymeric material with an additive; b)consolidating the blend; c) irradiating the highly crystalline polymericmaterial at temperature below the melt with ionizing radiation; d)heating the cross-linked blend to a temperature above the melting pointof the blend; e) pressurizing the cross-linked blend under at leastabout 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa; f) holding at this pressure; g) cooling the heatedthe cross-linked blend to about room temperature; and h) releasing thepressure to about an atmospheric pressure level, thereby forming a anoxidation-resistant highly crystalline cross-linked blend of polymer andadditive.

In one aspect, the invention provides methods of making a cross-linkedhighly crystalline blend of polymer and additive comprising: a) blendingpolymeric material with an additive; b) consolidating the blend; c)heating the blend to a temperature above the melting point of the blend;d) pressurizing the blend under at least about 10-1000 MPa, preferablyat least about 150 MPa, more preferably at least about 250 MPa; e)holding at this pressure; f) cooling the heated the blend to about roomtemperature; g) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline polymeric material; h)machining the polymeric material thereby forming a medical implant; andi) irradiating the medical implant at temperature below the melt withionizing radiation, thereby forming a highly crystalline cross-linkedmedical implant.

One aspect of the invention provides methods of making a cross-linkedhighly crystalline blend of polymer and additive comprising: a) blendingpolymeric material with an additive; b) consolidating the blend; c)pressurizing the blend under at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa; d) heatingthe pressurized the blend to a temperature of above 100° C. to below themelt of the pressurized blend; e) holding at this pressure; f) coolingthe heated the blend to about room temperature; g) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material; h) machining the polymericmaterial thereby forming a medical implant; and i) irradiating themedical implant at temperature below the melt with ionizing radiation,thereby forming a highly crystalline cross-linked medical implant.

In one aspect, invention provides methods of making oxidation-resistantcross-linked highly crystalline blend of polymer and additivecomprising: a) blending polymeric material with an additive; b)consolidating the blend; c) irradiating the highly crystalline polymericmaterial at temperature below the melt with ionizing radiation; d)heating the cross-linked blend to a temperature above the melting pointof the blend; e) pressurizing the cross-linked blend under at leastabout 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa; f) holding at this pressure; g) cooling the heatedthe cross-linked blend to about room temperature; h) releasing thepressure to about an atmospheric pressure level, thereby formingoxidation-resistant cross-linked highly crystalline cross-linked blendof polymer and additive; and i) machining the polymeric material,thereby forming oxidation-resistant highly crystalline cross-linkedmedical implant.

In another aspect, the highly crystalline cross-linked blend of polymerand additive is machined, thereby forming a medical implant. In anotheraspect, the highly crystalline cross-linked medical implant is packagedand sterilized by ionizing radiation or gas sterilization, therebyforming a sterile highly crystalline cross-linked medical implant.

In another aspect, the invention provides a method of making highlycrystalline blend of polymer with an additive comprising a plasticizingagent or a nucleating agent as additive.

In another aspect, the invention provides a method of makingoxidation-resistant highly cross-linked blend of polymer comprisingplasticizing the polymer with an additive like an antioxidantplasticizing agent, such as vitamin E.

In another aspect, the invention provides methods of makingoxidation-resistant highly crystalline cross-linked polymeric materialfurther comprising doping the highly crystalline cross-linked polymericmaterial with an antioxidant by diffusion, thereby formingantioxidant-doped highly crystalline cross-linked polymeric material.

In another aspect, the invention provides methods of making highlycrystalline cross-linked polymeric material further comprising: a)machining the highly crystalline cross-linked polymeric material,thereby forming a medical implant; and b) doping the medical implantwith an antioxidant by diffusion, thereby forming antioxidant-dopedhighly crystalline cross-linked medical implant.

In another aspect, the invention provides methods of making highlycrystalline cross-linked polymeric material further comprising: a)doping the highly crystalline cross-linked polymeric material with anantioxidant by diffusion, thereby forming antioxidant-doped highlycrystalline cross-linked polymeric material; and b) machining theantioxidant-doped highly crystalline cross-linked polymeric material,thereby forming antioxidant-doped highly crystalline cross-linkedmedical implant.

In one aspect, the antioxidant-doped highly crystalline cross-linkedmedical implant is packaged and sterilized by ionizing radiation or gassterilization, thereby forming a sterile and antioxidant-doped highlycrystalline cross-linked medical implant.

In another aspect, the invention provides methods of making highlycrystalline cross-linked polymeric material further comprising: a)pressurizing the polymeric material under at least about 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; b) heating the pressurized polymeric material to a temperature ofabove 100° C. to below the melt of the pressurized polymeric material;c) cooling the heated polymeric material to about room temperature; d)releasing the pressure to about an atmospheric pressure level; e) dopingthe polymeric material with an antioxidant by diffusion, thereby formingantioxidant-doped polymeric material; and f) irradiating theantioxidant-doped polymeric material at temperature below the melt withionizing radiation, thereby forming antioxidant-doped highly crystallinecross-linked polymeric material.

In another aspect, the invention provides methods of making a highlycrystalline cross-linked polymeric material further comprising: a)pressurizing the polymeric material under at least about 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; b) heating the pressurized polymeric material to a temperature ofabove 100° C. to below the melt of the pressurized polymeric material;c) cooling the heated polymeric material to about room temperature; d)releasing the pressure to about an atmospheric pressure level; e)machining the highly crystalline polymeric material, thereby forming amedical implant; f) doping the medical implant with an antioxidant bydiffusion, thereby forming antioxidant-doped medical implant; and g)irradiating the antioxidant-doped medical implant at temperature belowthe melt with ionizing radiation, thereby forming antioxidant-dopedhighly crystalline cross-linked polymeric material.

In another aspect, the invention provides a method of makingoxidation-resistant highly crystalline cross-linked polymeric materialcomprising: a) doping the polymeric material (such as UHMWPE) with anantioxidant by diffusion, thereby forming an antioxidant-doped polymericmaterial; b) irradiating the antioxidant-doped polymeric material at atemperature below the melting point with ionizing radiation, therebyforming an antioxidant-doped cross-linked polymeric material; c) heatingthe antioxidant-doped cross-linked polymeric material to a temperatureabove the melting point; d) pressuring the polymeric material to atleast about 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa; e) holding at this pressure; f)cooling the heated polymeric material to about room temperature; and g)releasing the pressure to about an atmospheric pressure level, therebyforming an antioxidant-doped, cross-linked, highly crystalline polymericmaterial.

In another aspect, the invention provides a method of makingoxidation-resistant highly crystalline cross-linked polymeric materialcomprising: a) doping the polymeric material (such as UHMWPE) with anantioxidant by diffusion, thereby forming an antioxidant-doped polymericmaterial; b) irradiating the antioxidant-doped polymeric material at atemperature below the melt with ionizing radiation, thereby forming anantioxidant-doped cross-linked polymeric material; c) pressurizing thecross-linked polymeric material under at least about 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; d) heating the pressurized cross-linked polymeric material to atemperature of above 100° C. to below the melting point of thepressurized cross-linked polymeric material; e) holding at the pressureand temperature; f) cooling the heated polymeric material to about roomtemperature; and g) releasing the pressure to about an atmosphericpressure level, thereby forming an antioxidant-doped cross-linked highlycrystalline polymeric material.

In another aspect, the invention provides a method of making highlycrystalline cross-linked polymeric material further comprising: a)heating the polymeric material to a temperature above the melt; b)pressurizing the heated polymeric material under at least about 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; c) cooling the heated polymeric material to about roomtemperature; d) releasing the pressure to about an atmospheric pressurelevel; e) doping the polymeric material with an antioxidant bydiffusion, thereby forming an antioxidant-doped polymeric material; andf) irradiating the antioxidant-doped polymeric material at temperaturebelow the melt with ionizing radiation, thereby forming anantioxidant-doped highly crystalline cross-linked polymeric material.

In another aspect, the invention provides methods of making highlycrystalline cross-linked polymeric material comprising: a) heating thepolymeric material to a temperature above the melt; b) pressurizing theheated polymeric material under at least about 10-1000 MPa, preferablyat least about 150 MPa, more preferably at least about 250 MPa; c)cooling the heated polymeric material to about room temperature; d)releasing the pressure to about an atmospheric pressure level; e)machining the highly crystalline polymeric material, thereby forming amedical implant; f) doping the medical implant with an antioxidant bydiffusion, thereby forming antioxidant-doped medical implant; and g)irradiating the antioxidant-doped medical implant at temperature belowthe melt with ionizing radiation, thereby forming antioxidant-dopedhighly crystalline cross-linked polymeric material.

In another aspect, the antioxidant-doped highly crystalline cross-linkedpolymeric material is machined, thereby forming a medical implant.

In another aspect, the antioxidant-doped highly crystalline cross-linkedmedical implant is washed, packaged and sterilized by ionizing radiationor gas sterilization, thereby forming a sterile and antioxidant-dopedhighly crystalline cross-linked medical implant.

In one aspect, before packaging and sterilization, the antioxidant-dopedhighly crystalline cross-linked medical implant is washed in anindustrial washing machine with detergent. In another aspect, beforepackaging and sterilization, the antioxidant-doped highly crystallinecross-linked medical implant is washed by soaking in a solvent, such asethanol.

In another aspect, the antioxidant-doped highly crystalline cross-linkedpolymeric material is washed, then machined, thereby forming a medicalimplant.

In another aspect, the antioxidant-doped highly crystalline cross-linkedmedical implant is packaged and sterilized by ionizing radiation or gassterilization, thereby forming a sterile and antioxidant-doped highlycrystalline cross-linked medical implant.

In another aspect, the antioxidant-doped highly crystalline cross-linkedmedical implant is packaged and sterilized by gas sterilization, therebyforming a sterile and antioxidant-doped highly crystalline cross-linkedmedical implant.

In another aspect, the highly crystalline and antioxidant-doped medicalimplant is packaged and irradiated with ionizing radiation to aradiation dose of more than 1 kGy, such as about 25-400 kGy or more, tocross-link and sterilize the medical implant. Preferably the radiationdose level is above 75 kGy, more preferably above 100 kGy, and yet morepreferably about 150 kGy.

In one aspect, the polymeric material is heated to a temperature abovethe melting point of the pressurized polymeric material, for example, at150° C., 180° C., 225° C., 300° C., or 320° C., and any temperaturetherebetween or thereabout as long as the temperature is below thethermal decomposition point.

In another, aspect, the invention provides a method of makingoxidation-resistant highly crystalline cross-linked polymeric materialcomprising: a) heating a polymeric material to a temperature above themelt; b) pressurizing the heated polymeric material under at least about10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; c) holding at this pressure; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto about an atmospheric pressure level, thereby forming a highlycrystalline polymeric material; f) irradiating the highly crystallinepolymeric material at a temperature below the melt with ionizingradiation, thereby forming a highly crystalline cross-linked polymericmaterial, g) doping with an antioxidant, such as vitamin E, therebyforming an antioxidant-doped highly crystalline cross-linked polymericmaterial; h) mechanically deforming the antioxidant-doped highlycrystalline cross-linked polymeric material below its melting point; andi) annealing the mechanically deformed antioxidant-doped polymericmaterial at a temperature below the melting point.

In another aspect, the invention provides a method of making anoxidation-resistant highly crystalline cross-linked polymeric materialcomprising: a) pressurizing a polymeric material under at least about10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; b) heating the pressurized polymeric material to atemperature above 100° C. to below the melt of the pressurized polymericmaterial; c) holding at this pressure; d) cooling the heated polymericmaterial to about room temperature; e) releasing the pressure to aboutan atmospheric pressure level, thereby forming a highly crystallinepolymeric material; f) irradiating the highly crystalline polymericmaterial at a temperature below the melt with ionizing radiation,thereby forming a highly crystalline cross-linked polymeric material; g)doping with an antioxidant, such as vitamin E, thereby forming anantioxidant-doped highly crystalline cross-linked polymeric material; h)mechanically deforming the antioxidant-doped highly crystallinecross-linked polymeric material below its melting point; and i)annealing the mechanically deformed antioxidant-doped polymeric materialat a temperature below the melting point.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymer andadditive comprising: a) blending polymeric material with an additive; b)consolidating the blend; c) heating the blend to a temperature above themelting point of the blend; d) pressurizing the blend under at leastabout 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa; e) holding at this pressure; f) cooling the heatedthe blend to about room temperature; g) releasing the pressure to aboutan atmospheric pressure level, thereby forming a highly crystallinepolymeric material; h) irradiating the highly crystalline polymericmaterial at temperature below the melt with ionizing radiation, therebyforming oxidation-resistant highly crystalline cross-linked blend ofpolymer and additive; i) doping with an antioxidant, such as vitamin E,thereby forming antioxidant-doped highly crystalline cross-linked blend;j) mechanically deforming the antioxidant-doped highly crystallinecross-linked blend below its melting point; and k) annealing themechanically deformed antioxidant-doped blend at a temperature below themelting point.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymer andadditive comprising: a) blending polymeric material with an additive; b)consolidating the blend; c) pressurizing the blend under at least about10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; d) heating the pressurized the blend to a temperaturebetween above 100° C. and below the melting point of the pressurizedblend; e) holding at this pressure; f) cooling the heated the blend toabout room temperature; g) releasing the pressure to about anatmospheric pressure level, thereby forming a highly crystallinepolymeric material; h) irradiating the highly crystalline polymericmaterial at temperature below the melt with ionizing radiation, therebyforming a highly crystalline cross-linked blend of polymer and additive;i) doping with an antioxidant, such as vitamin E, thereby forming anantioxidant-doped highly crystalline cross-linked blend; j) mechanicallydeforming the antioxidant-doped highly crystalline cross-linked blendbelow its melting point; and k) annealing the mechanically deformedantioxidant-doped blend at a temperature below the melting point.

In another aspect, the highly crystalline polymeric material isirradiated at a temperature between about room temperature and about 90°C., or at a temperature between about 90° C. and the peak melting pointof the highly crystalline polymeric material.

In another aspect, the irradiated polymeric material is annealed at atemperature below the melting point of the polymeric materials forexample, a temperature between about 90° C. and peak melting point ofthe irradiated polymeric material.

In another aspect, the polymeric material can be pressurized to aboveabout 150 MPa, for example, about 200 MPa, 250 MPa, 310 MPa, 300 MPa,320 MPa, 400 MPa, or 450 MPa.

Yet in another aspect, the invention provides medical implantscomprising the highly crystalline cross-linked and antioxidant-dopedhighly crystalline cross-linked polymeric material and highlycrystalline cross-linked polymer blend with an additive made asdescribed herein. In another aspect, the polymeric material iscompression molded to another piece or a medical implant, therebyforming an interface or an interlocked hybrid material. The medicalimplants, according to an aspect of the invention, comprises medicaldevices including acetabular liner, shoulder glenoid, patellarcomponent, finger joint component, ankle joint component, elbow jointcomponent, wrist joint component, toe joint component, bipolar hipreplacements, tibial knee insert, tibial knee inserts with reinforcingmetallic and polyethylene posts, intervertebral discs, sutures, tendons,heart valves, stents, vascular grafts.

According to one aspect, the invention provides radiation treated UHMWPEhaving more than 2 melting peaks and a crystallinity above about 50%. Inanother aspect, the invention provides finished products, for example,an article, a medical device or a medical prosthesis and the like,comprising UHMWPE, wherein the UHMWPE having at least two melting peaksand a crystallinity of at least about 50%. According to the invention,the UHMWPE or the finished product is doped with vitamin E, irradiatedto a dose of more than 1 kGy, such as about 25-400 kGy or more,preferably to about 150 kGy, and has detectable free radicals.

According to another aspect, the invention provides UHMWPE made byblending the UHMWPE powder with vitamin E, irradiating the vitamin Eblended UHMWPE, high pressure crystallizing the blend by heating to atemperature above the melting point of the irradiated UHMWPE at anambient pressure, pressurizing to at least about 10-1000 MPa, preferablyat least about 150 MPa, more preferably at least about 250 MPa, coolingto about room temperature while under pressure, and releasing thepressure. According to the invention, the UHMWPE is irradiated to a doseof more than 1 kGy, such as about 25-400 kGy or more, preferably toabout 150 kGy, and machined to form a finished product, for example, amedical implant and the like. The finished product can be packaged andsterilized.

According to another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymer(such as UHMWPE) and additive comprising: a) blending polymeric materialwith an additive; b) consolidating the blend; c) irradiating the highlycrystalline polymeric material at a temperature below the melt withionizing radiation, thereby providing a cross-linked blend of polymericmaterial and additive; d) pressurizing the cross-linked blend under atleast about 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa; e) heating the pressurizedcross-linked blend to a temperature above 100° C. to below the meltingpoint of the pressurized cross-linked blend; f) holding at this pressureand temperature; g) cooling the heated blend to about room temperature;and h) releasing the pressure to about an atmospheric pressure level,thereby forming a highly crystalline cross-linked blend of polymericmaterial and additive. According to the invention, the UHMWPE isirradiated to a dose of more than 1 kGy, such as about 25-400 kGy ormore, preferably to about 150 kGy, has detectable free radicals, and ismachined to form a finished product, for example, a medical implant andthe like. The finished product can be packaged and sterilized.

According to another aspect, the invention provides UHMWPE made byblending the UHMWPE powder with vitamin E, irradiating the vitamin Eblended UHMWPE, Pressurizing to at least 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa, heating toa temperature above the melting of the irradiated polyethylene atambient pressure, cooling to about room temperature while underpressure, and releasing the pressure. According to the invention, theUHMWPE is irradiated to a dose of more than 1 kGy, such as about 25-400kGy or more, preferably to about 150 kGy, has detectable free radicals,and is machined to form a finished product, for example, a medicalimplant and the like. The finished product can be packaged andsterilized.

According to another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymer(such as UHMWPE) and additive comprising: a) blending polymeric materialwith an additive; b) consolidating the blend; c) irradiating the highlycrystalline polymeric material at a temperature below the melt withionizing radiation, thereby providing a cross-linked blend of polymericmaterial and additive; d) machining the blend, thereby forming afinished product, for example, a medical implant and the like; e)heating the medical implant to a temperature above the melting point; f)pressuring the medical implant to at least 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa; g) holdingat this pressure; h) cooling the heated medical implant to about roomtemperature; and i) releasing the pressure to about an atmosphericpressure level, thereby forming antioxidant-doped cross-linked highlycrystalline medical implant. According to the invention, the UHMWPE isirradiated to a dose of more than 1 kGy, such as about 25-400 kGy ormore, preferably to about 150 kGy, has detectable free radicals, and ismachined to form a finished product, for example, a medical implant andthe like. The finished product can be packaged and sterilized.

According to another aspect, the invention provides UHMWPE made byblending the UHMWPE powder with vitamin E, irradiating the vitamin Eblended UHMWPE, forming a finished product, for example a medicalimplant, high pressure crystallizing the blend by heating to atemperature above the melting point of the irradiated polyethylene atambient pressure, pressurizing to at least 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa, cooling toabout room temperature while under pressure, and releasing the pressure.According to the invention, the UHMWPE is irradiated to a dose of morethan 1 kGy, such as about 25-400 kGy or more, preferably to about 150kGy, wherein the finished product is formed by consolidating the vitaminE-doped UHMWPE and by machining. In another aspect, the finished productis formed by direct compression molding the vitamin E-doped UHMWPE intoimplant shape, wherein the implant shape is a finished shape of theimplant or the implant shape may require further machining for afinished shape of the implant. The finished product can be packaged andsterilized.

According to another aspect, the invention provides UHMWPE made byblending the UHMWPE powder with vitamin E, irradiating the vitamin Eblended UHMWPE, forming a finished product, for example a medicalimplant, pressurizing to at least about 10-1000 MPa, preferably at leastabout 150 MPa, more preferably at least about 250 MPa, heating to atemperature above the melting point of the irradiated polyethylene atambient pressure, cooling to about room temperature, and releasing thepressure. According to the invention, the UHMWPE is irradiated to a doseof more than 1 kGy, such as about 25-400 kGy or more, preferably toabout 150 kGy, wherein the finished product has detectable freeradicals. The finished product can be formed by direct compressionmolding the vitamin E-doped UHMWPE into implant shape, wherein theimplant shape is a finished shape of the implant or the implant shapemay require further machining for a finished shape of the implant. Thefinished product can be packaged and sterilized.

According to another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymer(such as UHMWPE) and additive comprising: a) blending polymeric materialwith an additive; b) consolidating the blend; c) irradiating the highlycrystalline polymeric material at a temperature below the melt withionizing radiation, thereby providing a cross-linked blend of polymericmaterial and additive, d) machining the blend, thereby forming afinished product, for example, a medical implant and the like; e)pressurizing the implant under at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa; f) heatingthe pressurized implant to a temperature above 100° C. to below the meltof the pressurized implant; g) holding at this pressure and temperature;h) cooling the heated implant to about room temperature; and i)releasing the pressure to about an atmospheric pressure level, therebyforming a highly crystalline cross-linked medical implant. According tothe invention, the UHMWPE is irradiated to a dose of more than 1 kGy,such as about 25-400 kGy or more, preferably to about 150 kGy, hasdetectable free radicals, and is machined to form a finished product,for example, a medical implant and the like. The finished product can bepackaged and sterilized.

According to another aspect, the invention provides irradiated UHMWPE,wherein the UHMWPE is machined to form a finished product, for example,an article, an implant, or a medical prosthesis and the like, andwherein the finished product is high pressure crystallized. According tothe invention, the UHMWPE is irradiated to a dose of more than 1 kGy,such as about 25-400 kGy or more, preferably to about 150 kGy, morepreferably to about 65 kGy, wherein the UHMWPE is irradiated at aboveabout 80° C. and below the melting point of the irradiated UHMWPE,wherein the UHMWPE is melted before machining to form a finished productor an article. High pressure crystallization is carried out by heatingto a temperature above the melting point of the irradiated polyethyleneat ambient pressure, pressurizing to at least about 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa, heating to a temperature above the melting point of the irradiatedpolyethylene at ambient pressure, cooling to about room temperature, andreleasing the pressure. High pressure crystallization also can becarried out by pressurizing to at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa, heating toa temperature above the melting point of the irradiated polyethylene atambient pressure, cooling to about room temperature, and releasing thepressure. The finished product can be packaged and sterilized.

In another aspect, the invention provides methods of making across-linked highly crystalline polymeric material comprising: a)heating the polymeric material to a temperature above the melt; b)pressurizing the polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; c) holding at this pressure and temperature; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto about an atmospheric pressure level, thereby forming a highlycrystalline polymeric material; f) irradiating the polymeric-material ata temperature below the melt with ionizing radiation, thereby forming ahighly crystalline cross-linked polymeric material; g) pressuring thehighly crystalline highly cross-linked polymeric material under at least10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; h) heating the pressurized polymeric material to atemperature of above 100° C. to below the melt of the pressurized highlycrystalline, highly cross-linked polymeric material; i) holding at thispressure and temperature; j) cooling the heated polymeric material toabout room temperature; and k) releasing the pressure to about anatmospheric pressure level, thereby forming a highly crystalline highlycross-linked polymeric material.

In another aspect, the invention provides methods of making across-linked highly crystalline polymeric material comprising: a)pressuring the polymeric material under at least 10-1000 MPa, preferablyat least about 150 MPa, more preferably at least about 250 MPa; b)heating the pressurized polymeric material to a temperature of above100° C. to below the melt of the pressurized polymeric material; c)holding at this pressure and temperature; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto about an atmospheric pressure level, thereby forming a highlycrystalline polymeric material; f) irradiating the polymeric material ata temperature below the melt with ionizing radiation, thereby forming ahighly crystalline cross-linked polymeric material; g) pressuring thehighly crystalline, highly cross-linked polymeric material under atleast 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa; h) heating the pressurized polymeric material underat least about 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa; i) heating the pressurized polymericmaterial to a temperature of above 100° C. to below the melt of thepressurized highly crystalline, highly cross-linked polymeric material;j) holding at this pressure and temperature; k) cooling the heatedpolymeric material to about room temperature; and l) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline highly cross-linked polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline polymeric materialcomprising: a) heating the polymeric material to a temperature above themelt; b) pressurizing the polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; c) holding at this pressure and temperature; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto about an atmospheric pressure level, thereby forming a highlycrystalline polymeric material; f) irradiating the polymeric material ata temperature below the melt with ionizing radiation, thereby forming ahighly crystalline cross-linked polymeric material; and g) doping thehighly crystalline highly cross-linked polymeric material with anantioxidant by diffusion, thereby forming oxidation-resistant highlycrystalline highly cross-linked polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline polymeric materialcomprising: a) pressuring the polymeric material under at least 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; b) heating the pressurized polymeric material to a temperatureof above 100° C. to below the melt of the pressurized polymericmaterial; c) holding at this pressure and temperature; d) cooling theheated polymeric material to about room temperature; e) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material; f) irradiating the polymericmaterial at a temperature below the melt with ionizing radiation,thereby forming a highly crystalline cross-linked polymeric material;and g) doping the highly crystalline, highly cross-linked polymericmaterial with an antioxidant by diffusion, thereby formingoxidation-resistant highly crystalline highly cross-linked polymericmaterial.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline polymeric materialcomprising: a) heating the polymeric material to a temperature above themelt; b) pressurizing the polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; c) holding at this pressure and temperature; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto about an atmospheric pressure level, thereby forming a highlycrystalline polymeric material; f) irradiating the polymeric material ata temperature below the melt with ionizing radiation, thereby forming ahighly crystalline cross-linked polymeric material; g) mechanicallydeforming the highly crystalline highly cross-linked polymeric materialbelow its melting point; and h) annealing the mechanically deformedhighly crystalline highly crosslinked polymeric material at atemperature below the melting point, thereby forming oxidation-resistanthighly crystalline highly cross-linked polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline polymeric materialcomprising: a) pressuring the polymeric material under at least 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; b) heating the pressurized polymeric material to a temperatureof above 100° C. to below the melt of the pressurized polymericmaterial; c) holding at this pressure and temperature; d) cooling theheated polymeric material to about room temperature; e) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material; f) irradiating the polymericmaterial at a temperature below the melt with ionizing radiation,thereby forming a highly crystalline cross-linked polymeric material; g)mechanically deforming the highly crystalline highly cross-linkedpolymeric material below its melting point; and h) annealing themechanically deformed highly crystalline highly crosslinked polymericmaterial at a temperature below the melting point, thereby formingoxidation-resistant highly crystalline, highly cross-linked polymericmaterial.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymericmaterial and additive comprising: a) blending the polymeric materialwith an additive; b) consolidating the blend; c) heating the polymericmaterial to a temperature above the melt; d) pressurizing the polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; e) holding at this pressure andtemperature; f) cooling the heated polymeric material to about roomtemperature; g) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline polymeric material; h)irradiating the polymeric material at a temperature below the melt withionizing radiation, thereby forming a highly crystalline cross-linkedpolymeric material; i) heating the highly crystalline highlycross-linked blend to above the melt; j) pressuring the highlycross-linked blend under at least 10-1000 MPa, preferably at least about150 MPa, more preferably at least about 250 MPa; k) holding at thispressure and temperature; l) cooling the heated blend to about roomtemperature; and m) releasing the pressure to about an atmosphericpressure level, thereby forming oxidation-resistant highly crystallinehighly cross-linked blend of polymeric material and additive.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymericmaterial and additive comprising: a) blending the polymeric materialwith an additive; b) consolidating the blend; c) heating the polymericmaterial to a temperature above the melt; d) pressurizing the polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; e) holding at this pressure andtemperature; f) cooling the heated polymeric material to about roomtemperature; g) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline polymeric material; h)irradiating the polymeric material at a temperature below the melt withionizing radiation, thereby forming a highly crystalline cross-linkedpolymeric material; i) pressuring the highly crystalline highlycross-linked polymeric material under at least 10-1000 MPa, preferablyat least about 150 MPa, more preferably at least about 250 MPa; j)heating the pressurized polymeric material to a temperature of above100° C. to below the melt of the pressurized highly crystalline highlycross-linked polymeric material; k) holding at this pressure andtemperature; l) cooling the heated polymeric material to about roomtemperature; and m) releasing the pressure to about an atmosphericpressure level, thereby forming a highly crystalline highly cross-linkedblend of polymeric material and additive.

In another aspect, the invention provides methods of makingoxidation-resistant highly cross-linked highly crystalline blend ofpolymeric material and additive comprising: a) pressuring the polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; b) heating the pressurizedpolymeric material to a temperature of above 100° C. to below the meltof the pressurized polymeric material; c) holding at this pressure andtemperature; d) cooling the heated polymeric material to about roomtemperature; e) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline blend; f) irradiating theblend at a temperature below the melt with ionizing radiation, therebyforming a highly crystalline cross-linked blend; g) heating the highlycrystalline highly cross-linked blend to a temperature above the melt;h) pressurizing the highly cross-linked blend under at least 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; i) holding at this pressure and temperature; j) cooling theheated highly cross-linked blend to about room temperature; and k)releasing the pressure to about an atmospheric pressure level, therebyforming oxidation-resistant highly crystalline highly cross-linked blendof polymeric material and additive.

In another aspect, the invention provides methods of makingoxidation-resistant highly cross-linked highly crystalline blend ofpolymeric material and additive comprising: a) pressuring the polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; b) heating the pressurizedpolymeric material to a temperature of above 100° C. to below the meltof the pressurized polymeric material; c) holding at this pressure andtemperature; d) cooling the heated polymeric material to about roomtemperature; e) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline blend; f) irradiating theblend at a temperature below the melt with ionizing radiation, therebyforming a highly crystalline cross-linked blend; g) pressuring thehighly crystalline, highly cross-linked blend under at least 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; h) heating the pressurized cross-linked blend under at leastabout 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa; i) heating the pressurized cross-linked blend to atemperature of above 100° C. to below the melt of the pressurized highlycrystalline, highly cross-linked blend; j) holding at this pressure andtemperature; k) cooling the heated cross-linked blend to about roomtemperature; and l) releasing the pressure to about an atmosphericpressure level, thereby forming oxidation-resistant highly crystallinehighly cross-linked blend of polymeric material and additive.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymericmaterial and additive comprising: a) blending the polymeric materialwith an additive; b) consolidating the blend; c) heating the blend to atemperature above the melt; d) pressurizing the blend under at least10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; e) holding at this pressure and temperature; f) coolingthe heated blend to about room temperature; g) releasing the pressure toabout an atmospheric pressure level, thereby forming a highlycrystalline blend; h) irradiating the blend at a temperature below themelt with ionizing radiation, thereby forming a highly crystallinecross-linked blend; i) mechanically deforming the highly crystallinehighly cross-linked blend below its melting point; and j) annealing themechanically deformed highly crystalline highly crosslinked blend at atemperature below the melting point, thereby forming oxidation-resistanthighly crystalline highly cross-linked blend of polymeric material andadditive.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline blend of polymericmaterial and additive comprising: a) blending the polymeric materialwith an additive; b) consolidating the blend; c) pressuring the blendunder at least 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa; d) heating the pressurized blend to atemperature of above 100° C. to below the melt of the pressurized blend;e) holding at this pressure and temperature; f) cooling the heated blendto about room temperature; g) releasing the pressure to about anatmospheric pressure level, thereby forming a highly crystalline blend;h) irradiating the blend at a temperature below the melt with ionizingradiation, thereby forming a highly crystalline cross-linked blend; i)mechanically deforming the highly crystalline highly cross-linked blendbelow its melting point; and j) annealing the mechanically deformedhighly crystalline highly crosslinked blend at a temperature below themelting point, thereby forming oxidation-resistant highly crystallinehighly cross-linked blend of polymeric material and additive.

In another aspect, the invention provides methods of makingoxidation-resistant antioxidant-doped cross-linked highly crystallinepolymeric material comprising: a) doping the polymeric material with anantioxidant by diffusion; b) heating the antioxidant-doped polymericmaterial to a temperature above the melt; c) pressurizing theantioxidant-doped polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; d) holding at this pressure and temperature; e) cooling the heatedantioxidant-doped polymeric material to about room temperature; f)releasing the pressure to about an atmospheric pressure level, therebyforming a highly crystalline antioxidant-doped polymeric material; g)irradiating the antioxidant-doped polymeric material at a temperaturebelow the melt with ionizing radiation, thereby forming a highlycrystalline cross-linked antioxidant-doped polymeric material; h)heating the highly crystalline, highly cross-linked antioxidant-dopedpolymeric material to above the melt; i) pressuring the highlycross-linked antioxidant-doped polymeric material under at least 10-1000MPa, preferably at least about 150 MPa, more preferably at least about250 MPa; j) holding at this pressure and temperature; k) cooling theheated antioxidant-doped polymeric material to about room temperature;and l) releasing the pressure to about an atmospheric pressure level,thereby forming oxidation-resistant highly crystalline highlycross-linked antioxidant-doped polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant antioxidant-doped cross-linked highly crystallinepolymeric material comprising: a) doping the polymeric material with anantioxidant by diffusion; b) heating the antioxidant-doped polymericmaterial to a temperature above the melt; c) pressurizing theantioxidant-doped polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; d) holding at this pressure and temperature; e) cooling the heatedantioxidant-doped polymeric material to about room temperature; f)releasing the pressure to about an atmospheric pressure level, therebyforming a highly crystalline antioxidant-doped polymeric material; g)irradiating the antioxidant-doped polymeric material at a temperaturebelow the melt with ionizing radiation, thereby forming a highlycrystalline cross-linked antioxidant-doped polymeric material; h)pressuring the highly crystalline highly cross-linked antioxidant-dopedpolymeric material under at least 10-1000 MPa, preferably at least about150 MPa, more preferably at least about 250 MPa; i) heating thepressurized antioxidant-doped polymeric material to a temperature ofabove 100° C. to below the melt of the pressurized highly crystallinehighly cross-linked antioxidant-doped polymeric material; j) holding atthis pressure and temperature; k) cooling the heated antioxidant-dopedpolymeric material to about room temperature; and l) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline highly cross-linked antioxidant-doped polymericmaterial.

In another aspect, the invention provides methods of makingoxidation-resistant antioxidant-doped cross-linked highly crystallinepolymeric material comprising: a) doping the polymeric material with anantioxidant by diffusion; b) pressuring the antioxidant-doped polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; c) heating the pressurizedantioxidant-doped polymeric material to a temperature of above 100° C.to below the melt of the pressurized antioxidant-doped polymericmaterial; d) holding at this pressure and temperature; e) cooling theheated antioxidant-doped polymeric material to about room temperature;f) releasing the pressure to about an atmospheric pressure level,thereby forming a highly crystalline antioxidant-doped polymericmaterial; g) irradiating the blend at a temperature below the melt withionizing radiation, thereby forming a highly crystalline cross-linkedantioxidant-doped polymeric material; h) heating the highly crystallinehighly cross-linked antioxidant-doped polymeric material to atemperature above the melt; i) pressurizing the highly cross-linkedantioxidant-doped polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; j) holding at this pressure and temperature; k) cooling the heatedhighly cross-linked antioxidant-doped polymeric material to about roomtemperature; and l) releasing the pressure to about an atmosphericpressure level, thereby forming oxidation-resistant highly crystallinehighly cross-linked antioxidant-doped polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant antioxidant-doped cross-linked highly crystallinepolymeric material comprising: a) doping the polymeric material with anantioxidant by diffusion; b) pressuring the antioxidant-doped polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; c) heating the pressurizedantioxidant-doped polymeric material to a temperature of above 100° C.to below the melt of the pressurized antioxidant-doped polymericmaterial; d) holding at this pressure and temperature; e) cooling theheated antioxidant-doped polymeric material to about room temperature;f) releasing the pressure to about an atmospheric pressure level,thereby forming a highly crystalline antioxidant-doped polymericmaterial; g) irradiating the highly crystalline antioxidant-dopedpolymeric material at a temperature below the melt with ionizingradiation, thereby forming a highly crystalline cross-linkedantioxidant-doped polymeric material; h) pressuring the highlycrystalline, highly cross-linked antioxidant-doped polymeric materialunder at least 10-1000 MPa, preferably at least about 150 MPa, morepreferably at least about 250 MPa; i) heating the pressurizedcross-linked antioxidant-doped polymeric material under at least about10-1000 MPa, preferably at least about 150 MPa, more preferably at leastabout 250 MPa; j) heating the pressurized cross-linked antioxidant-dopedpolymeric material to a temperature of above 100° C. to below the meltof the pressurized highly crystalline, highly cross-linkedantioxidant-doped polymeric material; k) holding at this pressure andtemperature; l) cooling the heated cross-linked antioxidant-dopedpolymeric material to about room temperature; and m) releasing thepressure to about an atmospheric pressure level, thereby formingoxidation-resistant highly crystalline highly cross-linkedantioxidant-doped polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline antioxidant-dopedpolymeric material comprising: a) doping the polymeric material with anantioxidant by diffusion; b) heating the antioxidant-doped polymericmaterial to a temperature above the melt; c) pressurizing theantioxidant-doped polymeric material under at least 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa; d) holding at this pressure and temperature; e) cooling the heatedantioxidant-doped polymeric material to about room temperature; f)releasing the pressure to about an atmospheric pressure level, therebyforming a highly crystalline antioxidant-doped polymeric material; g)irradiating the antioxidant-doped polymeric material at a temperaturebelow the melt with ionizing radiation, thereby forming a highlycrystalline cross-linked antioxidant-doped polymeric material; h)mechanically deforming the highly crystalline, highly cross-linkedantioxidant-doped polymeric material below its melting point; and i)annealing the mechanically deformed highly crystalline highlycrosslinked antioxidant-doped polymeric material at a temperature belowthe melting point, thereby forming oxidation-resistant highlycrystalline, highly cross-linked antioxidant-doped polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant cross-linked highly crystalline antioxidant-dopedpolymeric material comprising: a) doping the polymeric material with anantioxidant by diffusion; b) pressuring the antioxidant-doped polymericmaterial under at least 10-1000 MPa, preferably at least about 150 MPa,more preferably at least about 250 MPa; c) heating the pressurizedantioxidant-doped polymeric material to a temperature of above 100° C.to below the melt of the pressurized antioxidant-doped polymericmaterial; d) holding at this pressure and temperature; e) cooling theheated antioxidant-doped polymeric material to about room temperature;f) releasing the pressure to about an atmospheric pressure level,thereby forming a highly crystalline antioxidant-doped polymericmaterial; g) irradiating the antioxidant-doped polymeric material at atemperature below the melt with ionizing radiation, thereby forming ahighly crystalline cross-linked antioxidant-doped polymeric material; h)mechanically deforming the highly crystalline, highly cross-linkedantioxidant-doped polymeric material below its melting point; and i)annealing the mechanically deformed highly crystalline, highlycrosslinked antioxidant-doped polymeric material at a temperature belowthe melting point, thereby forming oxidation-resistant highlycrystalline, highly cross-linked antioxidant-doped polymeric material.

In another aspect, the invention provides methods of makingoxidation-resistant highly cross-linked blend of polymeric material andadditive comprising: a) blending the polymeric material with anadditive; b) consolidating the blend; c) irradiating the blend at atemperature below the melt with ionizing radiation, thereby forming across-linked blend; d) mechanically deforming highly cross-linked blendbelow its melting point; and e) annealing the mechanically deformedhighly crosslinked blend at a temperature below the melting point,thereby forming oxidation-resistant highly cross-linked blend ofpolymeric material and additive.

In another aspect, the invention provides methods of makingoxidation-resistant highly cross-linked blend of polymeric material andadditive comprising: a) blending the polymeric material with anadditive; b) consolidating the blend; c) irradiating the blend at atemperature below the melt with ionizing radiation, thereby forming across-linked blend; d) mechanically deforming highly cross-linked blendbelow its melting point; and e) annealing the mechanically deformedhighly crosslinked blend at a temperature below the melting point,thereby forming oxidation-resistant highly cross-linked blend, f)pressurizing the oxidation-resistant, highly cross-linked blend to atleast 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa; g) heating the pressurized highly cross-linkedblend to a temperature of above 100° C. to below the melt of thepressurized highly cross-linked blend; h) holding at this pressure andtemperature; i) cooling the heated highly cross-linked blend to aboutroom temperature; and j) releasing the pressure to about an atmosphericpressure level, thereby forming oxidation-resistant highly crystallinehighly cross-linked blend of polymeric material and additive.

In another aspect, the invention provides UHMWPE made by heating to atemperature above the melting point, pressurizing to at least 10-1000MPa, preferably at least 150 MPa, more preferably at least 250 MPa,holding at this temperature, cooling to about room temperature,releasing the pressure, irradiating the high pressure crystallizedUHMWPE and then diffusing with an antioxidant such as vitamin E. Highpressure crystallization also can be carried out by pressurizing to atleast 10-1000 MPa, preferably at least 150 MPa, more preferably at least250 MPa, heating above 100° C. to below the melt of the pressurizedpolymeric material, holding at this pressure and temperature, cooling toabout room temperature and releasing the pressure. According to theinvention, the UHMWPE is irradiated to a dose of more than 1 kGy, suchas about 25-400 kGy or more, preferably to about 150 kGy, wherein thefinished product has detectable free radicals, wherein the finishedproduct is formed by direct compression molding of the vitamin E-dopedUHMWPE into implant shape, wherein the implant shape is a finished shapeof the implant or the implant shape may require further machining for afinished shape of the implant. The finished product can be packaged andsterilized.

In another aspect, the invention provides UHMWPE made by heating to atemperature above the melting point temperature, pressurizing to atleast 10-1000 MPa, preferably at least 150 MPa, more preferably at least250 MPa, holding at this temperature, cooling to room temperature,releasing the pressure, irradiating the high pressure crystallizedUHMWPE, mechanically deforming the high pressure crystallized UHMWPEbelow the melt and annealing at a temperature below the melt. Highpressure crystallization also can be carried out by pressurizing to atleast 10-1000 MPa, preferably at least 150 MPa, more preferably at least250 MPa, heating above 100° C. to below the melt of the pressurizedpolymeric material, holding at this pressure and temperature, cooling toabout room temperature and releasing the pressure. According to theinvention, the UHMWPE is irradiated to a dose of more than 1 kGy, suchas about 25-400 kGy or more, preferably to about 150 kGy, wherein thefinished product has no detectable free radicals. The finished productcan be machined to form a medical device. The medical device can bepackaged and sterilized.

In another aspect, the invention provides UHMWPE made by diffusing anantioxidant such as vitamin E, heating to a temperature above themelting point temperature, pressurizing to at least 10-1000 MPa,preferably at least 150 MPa, more preferably at least 250 MPa, holdingat this temperature, cooling to about room temperature, releasing thepressure, irradiating the high pressure crystallized UHMWPE,mechanically deforming the high pressure crystallized UHMWPE below themelt and annealing at a temperature below the melt. High pressurecrystallization also can be carried out by pressurizing to at least10-1000 MPa, preferably at least 150 MPa, more preferably at least 250MPa, heating above 100° C. to below the melt of the pressurizedpolymeric material, holding at this pressure and temperature, cooling toabout room temperature and releasing the pressure. According to theinvention, the UHMWPE is irradiated to a dose of more than 1 kGy, suchas about 25-400 kGy or more, preferably to about 150 kGy, wherein thefinished product has no detectable free radicals. The finished productcan be machined to form a medical device. The medical device can bepackaged and sterilized.

In another aspect, the invention provides UHMWPE made by diffusing anantioxidant such as vitamin E, heating to a temperature above themelting point temperature, pressurizing to at least 10-1000 MPa,preferably at least 150 MPa, more preferably at least 250 MPa, holdingat this temperature, cooling to about room temperature, releasing thepressure, irradiating the high pressure crystallized UHMWPE, heating toa temperature above the melting point temperature, pressurizing to atleast 10-1000 MPa, preferably at least 150 MPa, more preferably at least250 MPa, holding at this temperature, cooling to room temperature, andreleasing the pressure. High pressure crystallization also can becarried out by pressurizing to at least 10-1000 MPa, preferably at least150 MPa, more preferably at least 250 MPa, heating above 100° C. tobelow the melt of the pressurized polymeric material, holding at thispressure and temperature, cooling to about room temperature andreleasing the pressure. According to the invention, the UHMWPE isirradiated to a dose of more than 1 kGy, such as about 25-400 kGy ormore, preferably to about 150 kGy. The finished product can be machinedto form a medical device. The medical device can be packaged andsterilized.

Unless otherwise defined, all technical and scientific terms used hereinin their various grammatical forms have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. Although methods and materials similar to those describedherein can be used in the practice or testing of the present invention,the preferred methods and materials are described below. In case ofconflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and are not limiting.

Further features, objects, and advantages of the present invention areapparent in the claims and the detailed description that follows. Itshould be understood, however, that the detailed description and thespecific examples, while indicating preferred aspects of the invention,are given by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows schematically the high-pressure crystallization process andphases of polyethylene under various temperature and pressureconditions.

FIG. 2 schematically shows various steps and methods of making highlycrystalline oxidation-resistant cross-linked polymeric material.

FIG. 3 shows α-tocopherol profile in UHMWPE doped for 96 hours andannealed for 96 hours at 132° C.

FIG. 4 depicts DSC thermograms of a conventional and a high pressurecrystallized conventional unirradiated polyethylene.

FIG. 5 shows an optical micrograph of a cylindrical cross-section of ahigh pressure crystallized conventional polyethylene.

FIG. 6 depicts DSC thermograms of a warm irradiated/melted and a highpressure crystallized warm irradiated/melted polyethylene.

FIGS. 7A, 7B, and 7C depict scanning electron micrographs of (a) opaque(7A), (b) transparent (7B), and (c) transition between opaque andtransparent (7C), respectively, sections of high pressure crystallizedconventional UHMWPE.

FIG. 8 shows crystallinity of various high pressure crystallized,irradiated, and control UHMWPEs.

FIG. 9 shows Oxidation Index as a function of distance away from thesurface of accelerated aged 100-kGy irradiated, α-T-92 and α-T-127samples. The curves represent splined averages of three test samples.

FIG. 10 shows average maximum oxidation levels for unaged and aged highpressure crystallized, 100-kGy e-beam irradiated, and α-tocopherol dopedUHMWPE. Doping was done in air for 16 hours at room temperature and at100° C. Corresponding thermal controls also were kept at roomtemperature and at 100° C., respectively, for 16 hours in air withoutdoping.

FIG. 11 depicts splined averages (n=3) of the oxidation profiles of highpressure crystallized, 100-kGy irradiated, α-tocopherol doped, andaccelerated aged UHMWPEs.

FIG. 12 indicates Pin-on-Disk (POD) wear rates of unaged and agedVitamin E doped and undoped samples.

FIG. 13 shows the wear rates of unaged, just accelerated aged andethanol extracted and accelerated aged α-T-92 and α-T-127.

FIG. 14 shows the oxidation profiles of accelerated aged 111-kGyirradiated control and 111-kGy irradiated and α-tocopherol-doped andcleaned UHMWPE.

FIG. 15 shows α-tocopherol profile of 100-kGy irradiated UHMWPE, whichwas doped for 72 hours and annealed for 100 hours at 136° C.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides methods of making highly crystallineoxidation-resistant cross-linked polymeric material, medical implantsmade thereof, which comprise medical devices, including permanent andnon-permanent medical devices. The invention pertains to methods ofcrystallizing polyethylene, such as UHMWPE, under high pressure atelevated temperature, irradiating at different temperatures, doping thecross-linked polyethylene with an antioxidant. The invention alsopertains to methods of blending polyethylene with an additive, such asVitamin E, crystallizing the blend, irradiating at differenttemperatures including cold irradiation below the melt and subsequentmechanical annealing.

Polyethylene is a semi-crystalline material (55-60%) and contains foldedchain crystals when crystallized from the melt under ambient pressures.The majority of the crystals are in the orthorhombic phase with latticedimensions of 7.42, 4.95, and 2.55 Å for a, b and c dimensions,respectively. The unit cell axes are at 90° to each other. Deformationgives rise to the monoclinic phase with lattice dimensions of 8.09,4.79, and 2.55 Å. In the hexagonal phase, which is only encountered atpressures in excess of 300 MPa (see FIG. 1, for example), the unit celldimensions become 8.42, 4.56, and <2.55 Å. In this phase, the individualchain stems are rotated at random phase angles with respect to eachother allowing for chains to slide past each other to form a denselypacked structure. The crystals in this phase are termed the ‘ExtendedChain Crystals’ (ECC) because the dense packing allows the crystals togrow to a larger extent than folded chain crystals.

It is known that the crystallinity of uncross-linked UHMWPE can beincreased by high pressure and high temperature crystallization. Forinstance, when crystallized uncross-linked UHMWPE at pressures above 300MPa and 180° C. to obtain the hexagonal phase transition, the peakmelting point of the crystals, as determined by differential scanningcalorimetry (DSC), shifted to higher temperatures and the overallcrystallinity increased. Uncross-linked high pressure crystallizedpolyethylene with high crystallinity appeared to have higher fatigueresistance as a function of increasing crystallinity (see Baker et al.,Polymer, 2000. 41(2): p. 795-808). Therefore, an object of the inventionwas to achieve a highly cross-linked (25-1000 kGy) polyethylene withhigh crystallinity (>51%) and good oxidation resistance.

High toughness and high fatigue strength of polymers are attributed toenergy absorbing mechanisms such as cavitation and plastic deformation.The major energy absorbing mechanism in polyethylene is the plasticdeformation of the crystalline domains (crystal plasticity), whichdepends on ductility and crystallinity. Cross-linking polyethylene withhigh dose levels of irradiation drastically reduces the mobility of thechains, hence reducing the overall ductility. Melting in the presence ofcross-links limits the ability of the chains to reorder and hencedecreases the crystallinity of polyethylene. The combination of thesetwo factors, namely reduced chain mobility and reduced crystallinity,reduces cross-linked and melted polyethylene's fatigue resistance.

According to the invention, highly crystalline cross-linkedoxidation-resistant polyethylene can be obtained following variousprocesses and steps (see FIG. 2, for example), as described below, forexample:

1. High pressure crystallize unirradiated/uncross-linked polyethyleneusing either Route I or Route II:

-   -   A. Route I: Heat to the desired temperature, for example, above        the melt (for example, about 140° C., about 180° C., about 200°        C., about 250° C., or about 300° C.); then pressurize; then hold        pressure at about the same pressure, for one minute to a day or        more, preferably about 0.5 hours to 12 hours, more preferably 1        to 6 hours; then release the pressure (pressure has to be        released after cooling down to room temperature to avoid melting        of the crystals achieved under high pressure).    -   B. Route II: Pressurize to the desired pressure; then heat to        the desired temperature, for example, below the melt of        pressurized polyethylene (for example, about 150° C., about 180°        C., about 195° C., about 225° C., about 300° C., and about 320°        C.); then hold pressure at about the same pressure, for one        minute to a day or more, preferably about 0.5 hours to 12 hours,        more preferably 1 to 6 hours; then cool to room temperature;        then release the pressure (pressure has to be released after        cooling down to room temperature to avoid melting of the        crystals achieved under high pressure).

2. Then irradiate the high-pressure crystallized (HPC) polyethyleneusing either cold or warm irradiation:

-   -   A. Cold Irradiation (CI): irradiate at between about room        temperature and 90° C. using either e-beam or gamma radiation.        If the crystallinity of the HPC-polyethylene is too high, there        may not be enough amorphous polyethylene available for        cross-linking. Therefore, it may require higher than usual dose        levels, that is the dose levels required for polyethylene        crystallized without high-pressure (as described herein, for        example, usual dose levels of 75 kGy or 100 kGy), to achieve a        desired wear resistance or crosslink density.    -   B. Warm Irradiation (WI): irradiate at between about 90° C. and        the peak melting point of HPC-polyethylene, which is generally        around 145° C. The temperature of irradiation can be adjusted to        achieve a desired extent of amorphous polyethylene during        irradiation.

3. Then treat the irradiated HPC-polyethylene (I-HPC) by either one ofthe following methods or a combination thereof:

-   -   A. Repeat the high-pressure crystallization following Route I or        Route II, as described above.    -   B. Dope with an antioxidant, such as vitamin E, which can be        done by various ways, for example,        -   i. machine the final product, soak in vitamin E or its            solution at between room temperature and boiling point of            vitamin E solution; then wash, package and sterilize with            either gas plasma, ethylene oxide, or ionizing radiation,            such as gamma either in air or in inert gas.        -   ii. soak highly crystalline polymeric material in vitamin E            or its solution at between room temperature and boiling            point of vitamin E solution; machine medical implant, then            wash, package and irradiate packaged medical implant to            cross-link and sterilize.    -   C. Treat with a CIMA (Cold Irradiation and Mechanically        Annealed) method, for example,        -   i. heat to a temperature between 90° C. and peak melting            point of 1-HPC, deform under compression to a compression            ratio of above 2.5, hold deformation and cool to room            temperature, anneal at a temperature between 90° C. and peak            melting point of I-HPC, machine the final product, package            and sterilize, preferably sterilize with ethylene oxide or            gas plasma. CIMA methods can be applied as described in US            Patent publication 20030149125 (U.S. application Ser. No.            10/252,582), filed Sep. 24, 2002, the entirety of which is            hereby incorporated by reference.

In one aspect of the invention, the polymeric material is heated to atemperature above the melting point, for example, about 140° C., about180° C., about 200° C., about 250° C., or about 300° C. during the RouteI high pressure crystallization.

In another aspect, the polymeric material is heated to a temperaturebelow the melting point of the pressurized polymeric material, forexample, about 150° C., about 180° C., about 195° C., about 225° C.,about 300° C., and about 320° C. during the Route II high pressurecrystallization.

An antioxidant, which is compatible with lipophilic polyethylene, blendswell with and protects irradiated polyethylene against oxidation, atradiation doses as high as 100 kGy. Moreover, antioxidant was found notto interfere with cross-linking of polyethylene, when diffused afterirradiation. Therefore, cross-linked polyethylene diffused withantioxidant after irradiation showed wear rates comparable tocontemporary cross-linked and melted polyethylenes. Mechanicaldeformation at temperatures below the melt also is an alternativeapproach of removing residual free radicals from irradiated polyethylenewithout melting.

The present invention also provides methods of crystallizing a blend ofpolymer with an additive under a high pressure and high temperatures andirradiating thus formed highly crystalline blend to obtain a highlycrystalline, cross-linked blend of polymer and the additive. The presentinvention also provides methods of crystallizing a blend of polymer withadditive, which is also an antioxidant, under a high pressure and hightemperatures and irradiating thus formed highly crystalline blend toobtain a highly crystalline, cross-linked oxidation-resistant blend ofpolymer and an additive, which is also an antioxidant.

The present invention also provides methods of improving the oxidationresistance of highly crystalline cross-linked UHMWPE without melting.Melting of the highly crystalline UHMWPE will eliminate the ECC andreduce the crystallinity of the polymer. Therefore, the presentinvention provides the methods that use antioxidant or mechanicaldeformation below the melting point. According to the invention,improvement of oxidation resistance can be achieved either by dopingwith an antioxidant as described herein or by mechanical deformationmethods. The mechanical deformation is used after irradiation to reducethe population of residual free radicals without melting the polymer,for example, uniaxially compressing to a compression ratio of at least2.0 below the melting point (for example, less than about 150° C.) isutilized to reduce the residual free radical concentration. According tothe invention, orientation and some of the thermal stresses that canpersist following the mechanical deformation are reduced by furtherannealing at an elevated temperature below the melting point and coolingdown. Following annealing, it may be desirable to cool down thepolyethylene at slow enough cooling rate (for example, at about 10°C./hour) so as to minimize thermal stresses.

As described herein, it is demonstrated that mechanical deformation caneliminate residual free radicals in a radiation cross-linked UHMWPE. Theinvention also provides that one can first deform UHMWPE to a new shapeeither at solid- or at molten-state, for example, by compression.According to a process of the invention, mechanical deformation ofUHMWPE when conducted at a molten-state, the polymer is crystallizedunder load to maintain the new deformed shape. Following the deformationstep, the deformed UHMWPE sample is irradiated at a temperature belowthe melting point to crosslink, which generates residual free radicals.To reduce or eliminate these free radicals, the irradiated polymerspecimen is heated to a temperature below the melting point of thedeformed and irradiated polyethylene (for example, up to about 150° C.)to allow for the shape memory to partially recover the original shape.Generally, it is expected to recover about 80-90% of the original shape.During this recovery, the crystals undergo motion, which can help thefree radical recombination and elimination. The above process is termedas a ‘reverse-IBMA’. The reverse-IBMA (reverse-irradiation below themelt and mechanical annealing) technology can be a suitable process interms of bringing the technology to large-scale production ofUHMWPE-based medical devices.

In one aspect, the invention discloses medical implants, includingpermanent and non-permanent medical devices, comprising polymericmaterial having high crosslink density, high crystallinity, wear andoxidation resistance comparable with a highly cross-linked and meltedpolyethylene with fatigue resistance above highly cross-linked andmelted polyethylene.

Medical implants, as disclosed herein can be obtained by variousprocesses disclosed herein, for example, consolidating polymericmaterial; crystallizing the consolidated polymeric material under a hightemperature, such as at above 150° C. and at a high pressure, such as atabove 10-1000 MPa (for example, at least about 150 MPa, 200 MPa, 250MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or 450 MPa), preferably atleast about 150 MPa, more preferably at least about 250 MPa,subsequently, cooling down to room temperature followed by reducing thepressure to ambient, subsequently heating and holding the high pressurecrystallized polymeric material at a certain temperature, such as atbelow 150° C., so as to achieve partly amorphous polyethylene;irradiating by ionizing radiation to a dose of more than 1 kGy, such asabout 25-400 kGy or more, preferably to above about 75 kGy, morepreferably about 100 kGy; yet more preferably about 150 kGy; increasingthe oxidation resistance by either doping with an antioxidant ordecreasing the concentration of residual free radicals, for example, bymechanical deformation and annealing and/or crystallizing under highpressure and temperature.

Crystallization under high pressure can be done by first melting thepolyethylene at low pressure, subsequently pressurizing to above 10-1000MPa (for example, at least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300MPa, 320 MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,more preferably at least about 250 MPa, and cooling to about roomtemperature; or by first pressurizing to above 10-1000 MPa (for example,at least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400MPa, or 450 MPa), preferably at least about 150 MPa, more preferably atleast about 250 MPa, then increasing the temperature until orthorhombicto hexagonal phase transition occurs, then cooling down anddepressurizing.

The holding time in the melt, the holding time under pressure, theultimate temperature and pressure and the cooling rate can be changed toobtain the highest crystallinity and a roughly equal amount of extendedand folded chain crystals.

The temperature at which the folded chain crystals of the high pressurecrystallized polyethylene are melted and the holding time at thetemperature can be changed to obtain a desired ratio of extended tofolded chain crystals and amorphous content.

Irradiation cross-links the high pressure crystallized polyethylene andprovides wear resistance. Irradiation can be done at room temperature orat elevated temperatures below the melting point of polyethylene.Irradiation can be done in air, in vacuum, or in oxygen-freeenvironment, including inert gases such as nitrogen or noble gases.Irradiation can be done by using electron-beam, gamma irradiation, orx-ray irradiation.

The adverse oxidative effects of residual free radicals caused byionizing radiation are reduced by diffusing an antioxidant such asα-tocopherol into high pressure crystallized, partially melted andcross-linked polyethylene. The antioxidant prevents oxidation ofirradiated materials. Doping of polyethylene by an antioxidant isperformed as described herein.

The adverse oxidative effects of residual free radicals caused byionizing radiation is reduced by using a blend of polymer and additive,which is also an antioxidant, such as α-tocopherol to high pressurecrystallize and irradiate.

In another aspect, the residual free radicals caused by ionizingradiation are removed by mechanical annealing, where the polyethylene isheated to a temperature below the melting point (less than about 150°C.), preferably 145° C., more preferably at about 140° C. and deformedmechanically to provide mobility for the residual free radicals torecombine and stabilize.

In another aspect, the residual free radicals generated during ionizingradiation is removed by heating polyethylene to melt. Melting of theirradiated polyethylene is used as part of high-pressure crystallizationsubsequent to irradiation.

A high crystalline polyethylene can be made by a process comprisinghigh-pressure crystallization of unirradiated polyethylene, followed byirradiation, and elimination of the free radicals generated during theprocess, with minimum compromise in the crystallinity achieved.

According to one aspect of the invention, polyethylene is pressurized toabove about 10-1000 MPa (for example, at least about 150 MPa, 200 MPa,250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or 450 MPa), preferably atleast about 150 MPa, more preferably at least 250 MPa, yet morepreferably to above 320 MPa, heated to either about 180 or about 225°C., held at that temperature and that pressure, cooled to roomtemperature, reduced pressure to ambient, and irradiated at roomtemperature. Subsequently, one of the following processes can beemployed in order to improve oxidation resistance of the high pressurecrystallized polyethylene: a) doping the high pressure crystallizedpolyethylene with an antioxidant, such as vitamin E; or b) mechanicallydeforming the high pressure crystallized polyethylene below its meltingpoint followed by annealing near its melting point, essentially applyingany of the CIMA methods, and c) heating to above the melting point,pressurizing to at least about 10-1000 MPa (for example, at least about150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or 450MPa), preferably at least about 150 MPa, more preferably at least 250MPa, yet more preferably above 320 MPa, holding at this temperature andpressure, cooling to about room temperature, reducing pressure toambient.

A potential draw-back of irradiating a highly crystalline polyethyleneat room temperature can be that the reduced concentration of amorphousphase, where cross-linking primarily takes place, in a polyethylene withincreased crystallinity can also reduce the concentration of crosslinksformed by irradiation. Therefore, it is preferable to irradiatepolyethylene at an elevated temperature where the polymer isapproximately 60% or less crystalline to increase the amorphous content.High pressure crystallized polyethylene exhibits two melting peaks, oneat about 137° C. and the other at above about 140° C. The second peak isformed during high-pressure crystallization and represents extendedchain crystals (larger ones). The following sequence of events isapplied according to one aspect of the invention: Heated to atemperature below 140° C. to melt some of the smaller crystals and alsocross-linked the regions that contain smaller crystals; irradiated atthis temperature (warm irradiation (WI)), then one of the followingprocesses are employed in order to improve oxidation resistance of thehigh pressure crystallized polyethylene:

a) doping the high-pressure crystallized polyethylene with anantioxidant, such as vitamin E;

b) mechanically deforming the high-pressure crystallized polyethylenebelow its melting point followed by annealing near its melting point,essentially applying any of the CIMA methods; and

c) melt by heating to above the melting point, then pressurizing to atleast about 10-1000 MPa (for example, at least about 150 MPa, 200 MPa,250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or 450 MPa), preferably atleast about 150 MPa, more preferably at least 250 MPa, yet morepreferably above 320 MPa, holding pressure and temperature aboutconstant, cooling to about room temperature, and reducing pressure toambient. The melting step of this process will eliminate the crystals;therefore, the process is followed by high-pressure crystallization toachieve a high level of crystallinity.

In one aspect of the invention, the doping of high pressure crystallizedpolyethylene can be carried out by diffusion of an antioxidant, forexample, α-tocopherol, such as vitamin E. According to one aspect of theinvention, diffusion of the antioxidant is accelerated by increasing thetemperature and/or pressure.

According to another aspect of the invention, an antioxidant isdelivered in various forms, including in a pure form, for example, aspure vitamin E, or dissolved in a solvent.

According to another aspect of the invention, the diffusion rate of anantioxidant into the polyethylene is increased by increasing theconcentration of the antioxidant solution, for example, a vitamin Esolution.

In accordance with another aspect of the invention, diffusion rate of anantioxidant into the polyethylene is increased by swelling the highpressure crystallized polyethylene in a supercritical fluid, forexample, in a supercritical CO₂, i.e., the temperature being above thesupercritical temperature, which is 31.3° C., and the pressure beingabove the supercritical pressure, which is 73.8 bar.

In general, for example, in case of vitamin E, as the antioxidant,mixing the resin powder, flakes, particles, or a mixture thereof, withvitamin E and consolidation thereafter result in changes in color ofpolymeric material to yellow. According to one of aspect of the instantinvention, doping subsequent to consolidation avoids the exposure ofvitamin E to high temperatures and pressures of consolidation andprevents the discoloration of the polymeric material.

Doping in the consolidated state also allows one to achieve a gradientof antioxidant in consolidated polymeric material. One can dope acertain thickness surface layer where the oxidation of the polymericmaterial in a medical device is of concern in terms of wear. This can beachieved by simply dipping or soaking finished devices, for example, afinished medical implant, for example, in pure vitamin E or in asolution of vitamin E at a given temperature and for a given amount oftime.

According to the methods described herein, an antioxidant, for example,vitamin E, can be doped into the high-pressure crystallized polymericmaterial before, during, or after irradiation.

It may be possible that the doped antioxidant can leach out of thepolymeric material used in fabrication of medical implants or medicaldevices either during storage prior to use or during in vivo service.For a permanent medical device, the in vivo duration can be as long asthe remaining life of the patient, which is the length of time betweenimplantation of the device and the death of the patient, for example,1-120 years. If leaching out of the antioxidant is an issue, theirradiation of the medical implant or medical device or irradiation ofany portion thereof can be carried out after doping the antioxidant.This can ensure cross-linking of the antioxidant to the host polymerthrough covalent bonds and thereby minimize or prevent loss ofantioxidant from the medical implant or the device.

According to another aspect of the invention, antioxidant-dopedpolymeric material or an antioxidant-doped medical implant can be washedin an industrial washer with detergent before packaging andsterilization. An industrial washer, for example, a washer/dryer such asa HAMO T-21 or a washer/disinfectant/dryer such as a HAMO M-100 (HAMOAG, Pieterlen, Switzerland) can be used.

According to another aspect of the invention, antioxidant-dopedpolymeric material; or an antioxidant-doped medical implant can besoaked in a solvent such as ethanol before packaging and sterilization.A solvent, in which the antioxidant dissolves, is chosen so that thecleaning environment can provide a conducive environment for removingthe antioxidant from the polymeric material. This decreases thepossibility of antioxidant leaching from the antioxidant-doped polymericmaterial. The solvent can be at room temperature or at elevatedtemperatures, under ambient pressure or under elevated pressures, stillor stirred. The time for the antioxidant-doped polymeric material ormedical implant in contact with the solvent can range from about an hourto at least as long as the time that the doping was done, preferablyless than 16 hours.

According to another aspect of the invention, polymeric material, forexample, resin powder, flakes, particles, or a mixture thereof, is mixedwith an antioxidant and then the mixture is consolidated. Theconsolidated antioxidant doped polymeric material (blend) can bemachined to use as a component in a medical implant or as a medicaldevice.

According to another aspect of the invention, high-pressure crystallizedpolymeric material, for example, high pressure crystallized resinpowder, molded sheet, blown films, tubes, balloons, flakes, particles,or a mixture thereof, can be doped with an antioxidant, for example,vitamin E in the form of α-Tocopherol, by diffusion. High pressurecrystallized polymeric material, for example, high pressure crystallizedUHMWPE can be soaked in 100% vitamin E or in a solution of α-Tocopherolin an alcohol, for example, ethanol or isopropanol. A solution ofα-Tocopherol, about 50% by weight in ethanol can be used to diffuse into UHMWPE in contact with a supercritical fluid, such as CO₂.

The invention also relates to the following processing steps tofabricate medical devices made out of highly cross-linked polyethyleneand containing metallic pieces such as bipolar hip replacements, tibialknee inserts with reinforcing metallic and polyethylene posts,intervertebral disc systems; and for any implant that contains a surfacethat cannot be readily sterilized by a gas sterilization method.

According to one aspect of the invention, the high pressure crystallizedpolyethylene component of a medical implant is in close contact withanother material (that is a non-modular implant), such as a metallicmesh or back, a non-metallic mesh or back, a tibial tray, a patellatray, or an acetabular shell, wherein the polyethylene, such as resinpowder, flakes and particles are directly compression molded to thesecounter faces. For example, a polyethylene tibial insert is manufacturedby compression molding of polyethylene resin powder to a tibial tray, toa metallic mesh or back or to a non-metallic mesh or back. In the lattercase, the mesh is shaped to serve as a fixation interface with the bone,through either bony in-growth or the use of an adhesive, such aspolymethylmethacrylate (PMMA) bone cement. These shapes are of variousforms including, acetabular liner, tibial tray for total orunicompartmental knee implants, patella tray, and glenoid component,ankle, elbow or finger component. Another aspect of the inventionrelates to mechanical interlocking of the molded polyethylene with theother piece(s), for example, a metallic or a non-metallic piece, thatmakes up part of the implant. The consolidated polyethylene withmetallic piece is then high-pressure crystallized (HPC) to achieve ahighly crystalline polyethylene. The HPC can is carried out by eitherfirst heating or pressurizing the non-modular implant.

The interface geometry is crucial in that polyethylene assumes thegeometry as its consolidated shape. Polyethylene has a remarkableproperty of ‘shape memory’ due to its very high molecular weight thatresults in a high density of physical entanglements. Followingconsolidation, plastic deformation introduces a permanent shape change,which attains a preferred high entropy shape when melted. This recoveryof the original consolidated shape is due to the ‘shape memory’, whichis achieved when the polyethylene is consolidated. Because of this shapememory, the mechanical interlock will remain intact-during and after thehigh-pressure crystallization of the non-modular implant.

Another aspect of the invention provides that following thehigh-pressure crystallization of the polyethylene that was molded to thecounterface with the mechanical interlock, the hybrid component isirradiated using ionizing radiation to a desired dose level, forexample, about 25 kGy to about 1000 kGy, preferably between about 50 kGyand about 150 kGy. Another aspect of the invention discloses that theirradiation step generates residual free radicals and therefore, amelting step is introduced thereafter to quench the residual freeradicals followed by another step of high-pressure crystallization.Since the polyethylene is first consolidated into the shape of theinterface, thereby setting a ‘shape memory’ of the polymer, thepolyethylene does not separate from the counterface during melting andsubsequent high-pressure crystallization step.

In another aspect of the invention, there are provided methods ofcross-linking polyethylene, to create a polyethylene-based medicaldevice, wherein the device is immersed in an oxidation-resistant mediumsuch as inert gas or inert fluid, wherein the medium is heated to abovethe melting point of the irradiated highly crystalline polyethylene, forexample, high pressure crystallized UHMWPE (above about 140° C.) toeliminate the crystalline matter and to allow therecombination/elimination of the residual free radicals. Because theshape memory of the compression molded polymer is set at themechanically interlocked interface and that memory is strengthened bythe cross-linking step, there is no significant separation at theinterface between the polyethylene and the counterface.

Another aspect of the invention provides that following the above stepsof free radical elimination, the interface between the metal and thepolymer become sterile due to the high irradiation dose level usedduring irradiation. When there is substantial oxidation on the outsidesurface of the HPC-polyethylene induced during the free radicalelimination step or irradiation step, the device surface can be furthermachined to remove the oxidized surface layer. In another aspect, theinvention provides that in the case of a post-melting machining of animplant, the melting step can be carried out in the presence of an inertgas.

Another aspect of the invention includes methods of sterilization of thefabricated device, wherein the device is further sterilized withethylene oxide, gas plasma, or the other gases, when the interface issterile but the rest of the component is not.

Irradiation of a Finished Product Made of a Blend of UHMWPE with anAdditive Followed by High-Pressure Crystallization:

According to one aspect of the invention, a finished product, forexample, an article, a medical device, or a medical prosthesis and thelike, is irradiated and then high pressure crystallized as follows:Polymeric material, for example, resin powder, flakes, particles, or amixture thereof, is mixed/blended with an additive, for example, anantioxidant, preferably vitamin E (preferably less than about 10%, morepreferably less than 5%, more preferably less than 0.3%, and yet morepreferably 0.1% vitamin E) and then form an article or a medial deviceby:

-   -   a. Consolidating the blend, preferably by adding a step to        anneal the consolidated blend to remove thermal stresses; and    -   b. Machining the blend to form a finished product; or    -   c. Direct compression molding the blend to form a finished        product.

The finished product is irradiated to at least 1 kGy, preferably about25 kGy to about 1000 kGy or more, more preferably a dose of about 25,50, 75, 100, 125, 150, 175, or 200 kGy by gamma, e-beam, or x-ray.

The irradiated finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Irradiation of a Finished Product Made of a Blend of UHMWPE with anAdditive Followed by High-Pressure Crystallization:

According to one aspect of the invention, a finished product, forexample, an article, a medical device, or a medical prosthesis and thelike, is irradiated and then high pressure crystallized as follows:Polymeric material, for example, resin powder, flakes, particles, or amixture thereof, is mixed/blended with an additive, for example, anantioxidant, preferably vitamin E (preferably less than about 10%, morepreferably less than 5%, more preferably less than 0.3%, and yet morepreferably 0.1% vitamin E) and then form an article or a medial deviceby:

-   -   a. Doping the polymeric material with an antioxidant by        diffusion; and    -   b. Machining the blend to form a finished product; or    -   c. Direct compression molding the blend to form a finished        product.

The finished product is irradiated to at least 1 kGy, preferably about25 kGy to about 1000 kGy or more, more preferably a dose of about 25,50, 75, 100, 125, 150, 175, or 200 kGy by gamma, e-beam, or x-ray.

The irradiated finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Irradiation of a Finished Product Made of a Blend of UHMWPE with anAdditive Followed by High-Pressure Crystallization:

According to one aspect of the invention, a finished product, forexample, an article, a medical device, or a medical prosthesis and thelike, is irradiated and then high pressure crystallized as follows:Polymeric material, for example, resin powder, flakes, particles, or amixture thereof, is mixed/blended with an additive, for example, anantioxidant, preferably vitamin E (preferably less than about 10%, morepreferably less than 5%, more preferably less than 0.3%, and yet morepreferably 0.1% vitamin E) and then form an article or a medial deviceby:

-   -   a. Machining the blend to form a finished product; or    -   b. Direct compression molding the blend to form a finished        product; and    -   c. Doping the finished product with an antioxidant by diffusion.

The finished product is irradiated to at least 1 kGy, preferably about25 kGy to about 1000 kGy or more, more preferably a dose of about 25,50, 75, 100, 125, 150, 175, or 200 kGy by gamma, e-beam, or x-ray.

The irradiated finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Irradiation, Melting, and Machining of a Finished Product Prior toHigh-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is irradiated, melted, machined, and then high pressurecrystallized as follows:

Polymeric material is irradiated, melted, and machined to form afinished product, for example, an article, a medical device, or amedical prosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Irradiation and Machining of a Finished Product Prior to High-PressureCrystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is irradiated, machined and then high pressure crystallized asfollows:

Polymeric material is irradiated and machined to form a finishedproduct, for example, an article, a medical device, or a medicalprosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Warm Irradiation, Melting, and Machining of a Finished Product Prior toHigh-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is warm irradiated, melted, machined, and then high pressurecrystallized as follows:

Polymeric material is warm irradiated to above room temperature, such asa temperature above about 80° C. and below the melting point of thepolymeric material. The warm irradiated polymeric material is melted,and machined to form a finished product, for example, an article, amedical device, or a medical prosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Warm Irradiation and Machining of a Finished Product Prior toHigh-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is warm irradiated, machined, and then high pressure crystallizedas follows:

Polymeric material is warm irradiated to above room temperature, such asa temperature above about 80° C. and below the melting point of thepolymeric material and machined to form a finished product, for example,an article, a medical device, or a medical prosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320        MPa, 400 MPa, or 450 MPa), preferably at least about 150 MPa,        more preferably at least about 250 MPa, heating to a temperature        above the melting point of the irradiated polyethylene under an        ambient pressure, cooling to about room temperature, and        releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Cold Irradiation and Mechanically Annealing (CIMA) and Machining of aFinished Product Prior to High-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is irradiated by a CIMA method, machined, and then high pressurecrystallized as follows:

Polymeric material is irradiated and mechanically deformed at anelevated temperature, such as above 90° C. and below 140° C. anddeformed under pressure until cooled down to room temperature, annealedabove room temperature, such as at above 90° C. and below 140° C. torecover the deformed state, and machined to form a finished product, forexample, an article, a medical device, or a medical prosthesis and thelike.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa, 320 MPa, 400 MPa, or        450 MPa), preferably at least about 150 MPa, more preferably at        least about 250 MPa, cooling to about room temperature while        under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 310 MPa, 300 MPa,        320-MPa, 400 MPa, or 450 MPa), preferably at least about 150        MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Definitions:

“High pressure crystallized” (HPC) refers to a state of a polymericmaterial that has undergone high-pressure crystallization process,according to the invention, as described herein.

“High-pressure crystallization” refers to a method of making highpressure crystallized polyethylene, according to the invention, asdescribed herein.

The term “highly crystalline” or “high crystallinity” refers to a stateof a material of at least about 51% crystallinity.

“Antioxidant” refers to what is known in the art as (see, for example,WO 01/80778, U.S. Pat. No. 6,448,315). Alpha- and delta-tocopherol;propyl, octyl, or dedocyl gallates; lactic, citric, and tartaric acidsand their salts; orthophosphates, tocopherol acetate. Preferably vitaminE.

“Supercritical fluid” refers to what is known in the art, for example,supercritical propane, acetylene, carbon dioxide (CO₂). In thisconnection the critical temperature is that temperature above which agas cannot be liquefied by pressure alone. The pressure under which asubstance may exist as a gas in equilibrium with the liquid at thecritical temperature is the critical pressure. Supercritical fluidcondition generally means that the fluid is subjected to such atemperature and such a pressure that a supercritical fluid and thereby asupercritical fluid mixture is obtained, the temperature being above thesupercritical temperature, which for CO₂ is 31.3° C., and the pressurebeing above the supercritical pressure, which for CO₂ is 73.8 bar. Morespecifically, supercritical condition refers to a condition of amixture, for example, UHMWPE with an antioxidant, at an elevatedtemperature and pressure, when a supercritical fluid mixture is formedand then evaporate CO₂ from the mixture, UHMWPE doped with anantioxidant is obtained (see, for example, U.S. Pat. No. 6,448,315 andWO 02/26464)

The term “compression molding” as referred herein related generally towhat is known in the art and specifically relates to high temperaturemolding polymeric material wherein polymeric material is in any physicalstate, including powder form, is compressed into a slab form or mold ofa medical implant, for example, a tibial insert, an acetabular liner, aglenoid liner, a patella, or an unicompartmental insert.

The term “direct compression molding” as referred herein relatedgenerally to what is known in the art and specifically relates tomolding applicable in polyethylene-based devices, for example, medicalimplants wherein polyethylene in any physical state, including powderform, is compressed to solid support, for example, a metallic back,metallic mesh, or metal surface containing grooves, undercuts, orcutouts. The compression molding also includes high temperaturecompression molding of polyethylene at various states, including resinpowder, flakes and particles, to make a component of a medical implant,for example, a tibial insert, an acetabular liner, a glenoid liner, apatella, or an unicompartmental insert, to the counterface.

The term “mechanically interlocked” refers generally to interlocking ofpolyethylene and the counterface, that are produced by various methods,including compression molding, heat and irradiation, thereby forming aninterlocking interface, resulting into a ‘shape memory’ of theinterlocked polyethylene. Components of a device having such aninterlocking interface can be referred to as a “hybrid material”.Medical implants having such a hybrid material, contain a substantiallysterile interface.

The term “substantially sterile” refers to a condition of an object, forexample, an interface or a hybrid material or a medical implantcontaining interface(s), wherein the interface is sufficiently sterileto be medically acceptable, i.e., will not cause an infection or requirerevision surgery.

“Metallic mesh” refers to a porous metallic surface of various poresizes, for example, 0.1-3 mm. The porous surface can be obtained throughseveral different methods, for example, sintering of metallic powderwith a binder that is subsequently removed to leave behind a poroussurface; sintering of short metallic fibers of diameter 0.1-3 mm; orsintering of different size metallic meshes on top of each other toprovide an open continuous pore structure.

“Bone cement” refers to what is known in the art as an adhesive used inbonding medical devices to bone. Typically, bone cement is made out ofpolymethylmethacrylate (PMMA).

“High temperature compression molding” refers to the compression moldingof polyethylene in any form, for example, resin powder, flakes orparticles, to impart new geometry under pressure and temperature. Duringthe high temperature (above the melting point of polyethylene)compression molding, polyethylene is heated to above its melting point,pressurized into a mold of desired shape and allowed to cool down underpressure to maintain a desired shape.

“Shape memory” refers to what is known in the art as the property ofpolyethylene, for example, an UHMWPE, that attains a preferred highentropy shape when melted. The preferred high entropy shape is achievedwhen the resin powder is consolidated through compression molding.

The phrase “substantially no detectable residual free radicals” refersto a state of a polyethylene component, wherein enough free radicals areeliminated to avoid oxidative degradation, which can be evaluated byelectron spin resonance (ESR). The phrase “detectable residual freeradicals” refers to the lowest level of free radicals detectable by ESR.The lowest level of free radicals detectable with state-of-the-artinstruments is about 10¹⁴ spins/gram and thus the term “detectable”refers to a detection limit of 10¹⁴ spins/gram by ESR.

The terms “about” or “approximately” in the context of numerical valuesand ranges refers to values or ranges that approximate or are close tothe recited values or ranges such that the invention can perform asintended, such as having a desired degree of crystallinity orcross-linking and/or a desired lack of free radicals, as is apparent tothe skilled person from the teachings contained herein. This is due, atleast in part, to the varying properties of polymer compositions. Thusthese terms encompass values beyond those resulting from systematicerror.

Polymeric Material:

Ultra-high molecular weight polyethylene (UHMWPE) refers to linearnon-branched chains of ethylene having molecular weights in excess ofabout 500,000, preferably above about 1,000,000, and more preferablyabove about 2,000,000. Often the molecular weights can reach about8,000,000 or more. By initial average molecular weight is meant theaverage molecular weight of the UHMWPE starting material, prior to anyirradiation. See U.S. Pat. No. 5,879,400, PCT/US99/16070, filed on Jul.16, 1999, PCT/US97/02220, filed Feb. 11, 1997, and US Patent publication20030149125 (U.S. application Ser. No. 10/252,582), filed Sep. 24, 2002.

The products and processes of this invention also apply to various typesof polymeric materials, for example, any polyolefin, includinghigh-density-polyethylene, low-density-polyethylene,linear-low-density-polyethylene, ultra-high molecular weightpolyethylene (UHMWPE), or mixtures thereof. Polymeric materials, as usedherein, also applies to polyethylene of various forms, for example,resin powder, flakes, particles, powder, or a mixture thereof, or aconsolidated form derived from any of the above.

The term “additive” refers to any material that can be added to a basepolymer in less than 50 v/v %. This material can be organic or inorganicmaterial with a molecular weight less than that of the base polymer. Anadditive can impart different properties to the polymeric material, forexample, it can be a plasticizing agent, a nucleating agent, or anantioxidant.

“Blending” generally refers to mixing of a polyolefin in itspre-consolidated form with an additive. If both constituents are solid,blending can be done by using a third component such as a liquid tomediate the mixing of the two components, after which the liquid isremoved by evaporating. If the additive is liquid, for example(X-tocopherol, then the solid can be mixed with large quantities ofliquid, then diluted down to desired concentrations with the solidpolymer to obtain uniformity in the blend. In the case where an additiveis also an antioxidant, for example vitamin E, or α-tocopherol, thenblended polymeric material is also antioxidant-doped. Polymericmaterial, as used herein, also applies to blends of a polyolefin and aplasticizing agent, for example a blend of UHMWPE resin powder blendedwith α-tocopherol and consolidated. Polymeric material, as used herein,also applies to blends of an additive, a polyolefin and a plasticizingagent, for example UHMWPE soaked in α-tocopherol.

“Plasticizing agent” refers to a what is known in the art, a materialwith a molecular weight less than that of the base polymer, for exampleα-tocopherol in polyethylene or low molecular weight polybutadiene inpolyethylene, in both cases polyethylene being the base polymer. Theplasticizing agent is typically added to the base polymer in less thanabout 20 weight percent. The plasticizing agent increases flexibilityand softens the polymeric material.

The term “plasticization” or “plasticizing” refers to the propertiesthat a plasticizing agent imparts on the polymeric material into whichit has been added. There properties may include but are not limited toincreased elongation at break, reduced stiffness, and increasedductility.

A “nucleating agent’ refers to an additive known in the art, an organicor inorganic material with a molecular weight less than that of the basepolymer, which increases the rate of crystallization in the polymericmaterial. Typically, organocarboxylic acid salts, for example calciumcarbonate, are good nucleation agents for polyolefins. Also, nucleatingagents are typically used in small concentrations such as 0.5 wt %.

Doping:

Doping refers to a process well known in the art (see, for example, U.S.Pat. Nos. 6,448,315 and 5,827,904). In this connection, doping generallyrefers to contacting a polymeric material with an antioxidant undercertain conditions, as set forth herein, for example, doping UHMWPE withan antioxidant under supercritical conditions. “Doping” also refers tointroducing a second component into the base polymeric material inquantities less than 50 v/v %. More specifically, doping refers tointroducing an antioxidant into a polymeric material, most often bydiffusion of the antioxidant from a surrounding media into the polymericmaterial. A polymeric material treated in such a way is termed as“antioxidant-doped” polymeric material. However, the process of dopingan antioxidant into a polymeric material is not limited to the diffusionprocess. The polymeric material can be ‘doped’; however, by otheradditives as well, such as a plasticizing agent, in which case thepolymeric material treated in such a way may be termed as ‘plasticizingagent-doped’.

More specifically, for example, HPC polymeric material can be doped withan antioxidant by soaking the material in a solution of the antioxidant.This allows the antioxidant to diffuse into the polymer. For instance,the material can be soaked in 100% antioxidant. The material also can besoaked in an antioxidant solution where a carrier solvent can be used todilute the antioxidant concentration. To increase the depth of diffusionof the antioxidant, the material can be doped for longer durations, athigher temperatures, at higher pressures, and/or in presence of asupercritical fluid.

The doping process can involve soaking of a polymeric material, medicalimplant or device with an antioxidant, such as vitamin E, for about anhour up to several days, preferably for about one hour to 24 hours, morepreferably for one hour to 16 hours. The antioxidant can be heated toroom temperature or up to about 160° C. and the doping can be carriedout at room temperature or up to about 160° C. Preferably, theantioxidant can be heated to 10° C. and the doping is carried out at 10°C.

To further increase the uniformity of antioxidant in the base polymericmaterial, the doped polymeric material is annealed below or above themelt. The annealing is preferably for about an hour up to several days,more preferably for about one hour to 24 hours, most preferably for onehour to 16 hours. The doped polymeric material can be heated to roomtemperature or up to about 160° C. and the annealing can be carried outat room temperature or up to about 160° C. Preferably, the dopedpolymeric material can be heated to 100° C. and the annealing is carriedout at 100° C.

The term “conventional UHMWPE” refers to commercially availablepolyethylene of molecular weights greater than about 500,000.Preferably, the UHMWPE starting material has an average molecular weightof greater than about 2 million.

By “initial average molecular weight” is meant the average molecularweight of the UHMWPE starting material, prior to any irradiation.

Cross-Linking Polymeric Material:

Polymeric Materials, for example, UHMWPE can be cross-linked by avariety of approaches, including those employing cross-linking chemicals(such as peroxides and/or silane) and/or irradiation. Preferredapproaches for cross-linking employ irradiation. Cross-linked UHMWPE canbe obtained according to the teachings of U.S. Pat. No. 5,879,400,PCT/US99/16070, filed on Jul. 16, 1999, PCT/US97/02220, filed Feb. 11,1997, US Patent Publication 20030149125 (U.S. application Ser. No.10/252,582), filed Sep. 24, 2002, and U.S. Pat. No. 6,641,617, theentirety of which are hereby incorporated by reference.

Consolidated Polymeric Material:

Consolidated polymeric material refers to a solid, consolidated barstock, solid material machined from stock, or semi-solid form ofpolymeric material derived from any forms as described herein, forexample, resin powder, flakes, particles, or a mixture thereof, that canbe consolidated. The consolidated polymeric material also can be in theform of a slab, block, solid bar stock, machined component, film, tube,balloon, pre-form, implant, or finished medical device.

By “crystallinity” is meant the fraction of the polymer that iscrystalline. The crystallinity is calculated by knowing the weight ofthe sample (weight in grams), the heat absorbed by the sample in melting(E, in J/g) and the heat of melting of polyethylene crystals (ΔH=291J/g), and using the following equation:% Crystallinity=E/w·ΔH

By tensile “elastic modulus” is meant the ratio of the nominal stress tocorresponding strain for strains as determined using the standard testASTM 638 M III and the like or their successors.

The term “non-permanent device” refers to what is known in the art as adevice that is intended for implantation in the body for a period oftime shorter than several months. Some non-permanent devices could be inthe body for a few seconds to several minutes, while other may beimplanted for days, weeks, or up to several months. Non-permanentdevices include catheters, tubing, intravenous tubing, and sutures, forexample.

“Permanent device” refers to what is known in the art that is intendedfor implantation in the body for a period longer than several months.Permanent devices include medical devices, for example, ace tabularliner, shoulder glenoid, patellar component, finger joint component,ankle joint component, elbow joint component, wrist joint component, toejoint component, bipolar hip replacements, tibial knee insert, tibialknee inserts with reinforcing metallic and polyethylene posts,intervertebral discs, sutures, tendons, heart valves, stents, andvascular grafts.

“Pharmaceutical compound”, as described herein, refers to a drug in theform of a powder, suspension, emulsion, particle, film, cake, or moldedform. The drug can be free-standing or incorporated as a component of amedical device.

The term “pressure chamber” refers to a vessel or a chamber in which theinterior pressure can be raised to levels above atmospheric pressure.

The term “packaging” refers to the container or containers in which amedical device is packaged and/or shipped. Packaging can include severallevels of materials, including bags, blister packs, heat-shrinkpackaging, boxes, ampoules, bottles, tubes, trays, or the like or acombination thereof. A single component may be shipped in severalindividual types of package, for example, the component can be placed ina bag, which in turn is placed in a tray, which in turn is placed in abox. The whole assembly can be sterilized and shipped. The packagingmaterials include, but not limited to, vegetable parchments, multi-layerpolyethylene, Nylon 6, polyethylene terephthalate (PET), and polyvinylchloride-vinyl acetate copolymer films, polypropylene, polystyrene, andethylene-vinyl acetate (EVA) copolymers.

The term “heat-shrinkable packaging” refers to plastic films, bags, ortubes that have a high degree of orientation in them. Upon applicationof heat, the packaging shrinks down as the oriented chains retract,often wrapping tightly around the medical device.

“Melt transition temperature” refers to the lowest temperature at whichall the crystalline domains in a material disappear.

“Melting point” refers to the peak melting temperature measured by adifferential scanning calorimeter at a heating rate of 10° C. per minutewhen heating from 200° C. to 220° C.

Medical implants containing factory-assembled pieces that are in closecontact with the polyethylene form interfaces. In most cases, theinterfaces are not readily accessible to EtO gas or the GP during a gassterilization process.

Irradiation:

In one aspect of the invention, the type of radiation, preferablyionizing, is used. According to another aspect of the invention, a doseof ionizing radiation ranging from about 25 kGy to about 1000 kGy isused. The radiation dose can be about 50 kGy, about 65 kGy, about 75kGy, about 100 kGy, about 200 kGy, about 300 kGy, about 400 kGy, about500 kGy, about 600 kGy, about 700 kGy, about 800 kGy, about 900 kGy, orabout 1000 kGy, or above 1000 kGy, or any integer or fractional valuethereabout or therebetween. Preferably, the radiation dose can bebetween about 50 kGy and about 200 kGy. These types of radiation,including x-ray, gamma and/or electron beam, kills or inactivatesbacteria, viruses, or other microbial agents potentially contaminatingmedical implants, including the interfaces, thereby achieving productsterility. The irradiation, which may be electron or gamma irradiation,in accordance with the present invention can be carried out in airatmosphere containing oxygen, wherein the oxygen concentration in theatmosphere is at least 1%, 2%, 4%, or up to about 22%, or any integerthereabout or therebetween. In another aspect, the irradiation can becarried out in an inert atmosphere, wherein the atmosphere contains gasselected from the group consisting of nitrogen, argon, helium, neon, orthe like, or a combination thereof. The irradiation also can be carriedout in a vacuum.

In accordance with a preferred feature of this invention, theirradiation may be carried out in a sensitizing atmosphere. This maycomprise a gaseous substance which is of sufficiently small molecularsize to diffuse into the polymer and which, on irradiation, acts as apolyfunctional grafting moiety. Examples include substituted orunsubstituted polyunsaturated hydrocarbons; for example, acetylenichydrocarbons such as acetylene; conjugated or unconjugated olefinichydrocarbons such as butadiene and (meth)acrylate monomers; sulphurmonochloride, with chloro-tri-fluoroethylene (CTFE) or acetylene beingparticularly preferred. By “gaseous” is meant herein that thesensitizing atmosphere is in the gas phase, either above or below itscritical temperature, at the irradiation temperature.

Metal Piece:

In accordance with the invention, the piece forming an interface withpolymeric material is, for example, a metal. The metal piece infunctional relation with polyethylene, according to the presentinvention, can be made of a cobalt chrome alloy, stainless steel,titanium, titanium alloy or nickel cobalt alloy, for example. Variousmetal types can also be found in U.S. Ser. No. 60/424,709, filed Nov. 8,2002 (PCT/US03/18053, filed Jun. 10, 2003, WO 2004000159).

Non-Metallic Piece:

In accordance with the invention, the piece forming an interface withpolymeric material is, for example, a non-metal. The non-metal piece infunctional relation with polyethylene, according to the presentinvention, can be made of ceramic material, for example.

Interface:

The term “interface” in this invention is defined as the niche inmedical devices formed when an implant is in a configuration where acomponent is in contact with another piece (such as a metallic or anon-metallic component), which forms an interface between the polymerand the metal or another polymeric material. For example, interfaces ofpolymer-polymer or polymer-metal are in medical prosthesis, such as,orthopedic joints and bone replacement parts, for example, hip, knee,elbow or ankle replacements. Various metal/non-metal types andinterfaces also can be found in U.S. Ser. No. 60/424,709, filed Nov. 8,2002 (PCT/US03/18053, filed Jun. 10, 2003, WO 2004000159), the entiretyof which is hereby incorporated by reference.

Inert Atmosphere:

The term “inert atmosphere” refers to an environment having no more than1% oxygen and more preferably, an oxidant-free condition that allowsfree radicals in polymeric materials to form cross links withoutoxidation during a process of sterilization. An inert atmosphere is usedto avoid O₂, which would otherwise oxidize the medical device comprisinga polymeric material, such as UHMWPE. Inert atmospheric conditions suchas nitrogen, argon, helium, or neon are used for sterilizing polymericmedical implants by ionizing radiation.

Inert atmospheric conditions such as nitrogen, argon, helium, neon, orvacuum are also used for sterilizing interfaces of polymeric-metallicand/or polymeric-polymeric in medical implants by ionizing radiation.

Inert atmospheric conditions also refers to a insert gas, inert fluid,or inert liquid medium, such as nitrogen gas or silicon oil.

Anoxic Environment:

“Anoxic environment” refers to an environment containing gas, such asnitrogen, with less than 21%-22% oxygen, preferably with less than 2%oxygen. The oxygen concentration in an anoxic environment also can be atleast 1%, 2%, 4%, 6%, 8%, 10%, 12% 14%, 16%, 18%, 20%, or up to about22%, or any integer or any integer or fractional value thereabout ortherebetween.

Vacuum:

The term “vacuum” refers to an environment having no appreciable amountof gas, which otherwise would allow free radicals in polymeric materialsto form cross links without oxidation during a process of sterilization.A vacuum is used to avoid O₂, which would otherwise oxidize the medicaldevice comprising a polymeric material, such as UHMWPE. A vacuumcondition can be used for sterilizing polymeric medical implants byionizing radiation.

A vacuum condition can be created using a commercially available vacuumpump. A vacuum condition also can be used when sterilizing interfaces ofpolymeric-metallic and/or polymeric-polymeric in medical implants byionizing radiation.

Residual Free Radicals:

“Residual free radicals” refers to free radicals that are generated whena polymer is exposed to ionizing radiation such as gamma or e-beamirradiation. While some of the free radicals recombine with each otherto from crosslinks, some become trapped in crystalline domains. Thetrapped free radicals are also known as residual free radicals.

According to one aspect of the invention, the levels of residual freeradicals in the polymer generated during an ionizing radiation (such asgamma or electron beam) is preferably determined using electron spinresonance and treated appropriately to reduce the free radicals throughrecombination.

Sterilization:

One aspect of the present invention discloses a process of sterilizationof medical implants containing polymeric material, such as cross-linkedUHMWPE. The process comprises sterilizing the medical implants byionizing sterilization with gamma or electron beam radiation, forexample, at a dose level ranging from about 25-70 kGy, or by gassterilization with ethylene oxide or gas plasma.

Another aspect of the present invention discloses a process ofsterilization of medical implants containing polymeric material, such ascross-linked UHMWPE. The process comprises sterilizing the medicalimplants by ionizing sterilization with gamma or electron beamradiation, for example, at a dose level ranging from about 25-200 kGy.The dose level of sterilization is higher than standard levels used inirradiation. This is to allow cross-linking or further cross-linking ofthe medical implants during sterilization.

The term “alpha transition” refers to a transitional temperature and isnormally around 90-95° C.; however, in the presence of a sensitizingenvironment that dissolves in polyethylene, the alpha transition may bedepressed. The alpha transition is believed (An explanation of the“alpha transition temperature” can be found in Anelastic and DielectricEffects in Polymeric Solids, pages 141-143, by N. G. McCrum, B. E. Readand G. Williams; J. Wiley and Sons, N.Y., N.Y., published 1967) toinduce motion in the crystalline phase, which is hypothesized toincrease the diffusion of the sensitizing environment into this phaseand/or release the trapped free radicals. Heating above the alphatransition will also increase the diffusion of the additive, such asplasticizing agent or the antioxidant into the base polymer.

The term “critical temperature” corresponds to the alpha transition ofthe polyethylene. The term “below melting point” or “below the melt”refers to a temperature below the melting point of a polyethylene, forexample, UHMWPE. The term “below melting point” or “below the melt”refers to a temperature less than 155° C., which may vary depending onthe melting temperature of the polyethylene. The term “above meltingpoint” or “above the melt” refers to a temperature above the meltingpoint of a polyethylene, for example, UHMWPE. The term “above meltingpoint” or “above the melt” refers to a temperature more than 145° C.,which may vary depending on the melting temperature of the polyethylene.The melting temperature of the polyethylene can be, for example, 155°C., 145° C., 140° C. or 135° C., which again depends on the propertiesof the polyethylene being treated, for example, extended chain crystals,crystallinity, molecular weight averages and ranges, batch variations,etc. For example, “above melting point” or “above the melt” of apolymeric material under high pressure during a high-pressurecrystallization process refers to a temperature at or above 150° C. Themelting temperature is typically measured using a differential scanningcalorimeter (DSC) at a heating rate of 100° C. per minute. The peakmelting temperature thus measured is referred to as melting point andoccurs, for example, at approximately 137° C. for some grades of UHMWPE.It may be desirable to conduct a melting study on the startingpolyethylene material in order to determine the melting temperature andto decide upon an irradiation and annealing temperature.

The term “annealing” refers to heating the polymer below its peakmelting point. Annealing time can be at least 1 minute to several weekslong. In one aspect the annealing time is about 4 hours to about 48hours, preferably 24 to 48 hours and more preferably about 24 hours. Theannealing time required to achieve a desired level of recovery followingmechanical deformation is usually longer at lower annealingtemperatures. “Annealing temperature” refers to the thermal conditionfor annealing in accordance with the invention.

The term “contacted” includes physical proximity with or touching suchthat the sensitizing agent can perform its intended function.Preferably, a polyethylene composition or pre-form is sufficientlycontacted such that it is soaked in the sensitizing agent, which ensuresthat the contact is sufficient. Soaking is defined as placing the samplein a specific environment for a sufficient period of time at anappropriate temperature, for example, soaking the sample in a solutionof an antioxidant. The environment is heated to a temperature rangingfrom room temperature to a temperature below the melting point of thematerial. The contact period ranges from at least about 1 minute toseveral weeks and the duration depending on the temperature of theenvironment.

The term “oxidation-resistant” refers to a state of polymeric materialhaving an oxidation index (A. U.) of less than about 0.5 following agingpolymeric materials for 5 weeks in air at 80° C. oven. Thus, anoxidation-resistant cross-linked polymeric material generally shows anA. U. of less than about 0.5 after the aging period.

“Oxidation index” refers to the extent of oxidation in polymericmaterial. Oxidation index is calculated by obtaining an infraredspectrum for the polymeric material and analyzing the spectrum tocalculate an oxidation index, as the ratio of the areas under the 1740cm⁻¹ carbonyl and 1370 cm⁻¹ methylene stretching absorbances aftersubtracting the corresponding baselines.

The term “Mechanical deformation” refers to deformation taking placebelow the melting point of the material, essentially ‘cold-working’ thematerial. The deformation modes include uniaxial, channel flow, uniaxialcompression, biaxial compression, oscillatory compression, tension,uniaxial tension, biaxial tension, ultra-sonic oscillation, bending,plane stress compression (channel die) or a combination of any of theabove. The deformation could be static or dynamic. The dynamicdeformation can be a combination of the deformation modes in small orlarge amplitude oscillatory fashion. Ultrasonic frequencies can be used.All deformations can be performed in the presence of sensitizing gasesand/or at elevated temperatures.

The term “deformed state” refers to a state of the polyethylene materialfollowing a deformation process, such as a mechanical deformation, asdescribed herein, at solid or at melt. Following the deformationprocess, deformed polyethylene at a solid state or at melt is be allowedto solidify/crystallize while still maintains the deformed shape or thenewly acquired deformed state.

“IBMA” refers to irradiation below the melt and mechanical annealing.“IBMA” also is referred to as “CIMA” (Cold Irradiation and MechanicallyAnnealed).

Sonication or ultrasonic at a frequency range between 10 and 100 kHz canbe used, with amplitudes on the order of 1-50 microns. The time ofsonication is dependent on the frequency and temperature of sonication.In one aspect, sonication or ultrasonic frequency ranged from about 1second to about one week, preferably about 1 hour to about 48 hours,more preferably about 5 hours to about 24 hours and yet more preferablyabout 12 hours.

The invention is further described by the following examples, which donot limit the invention in any manner.

EXAMPLES Example 1 Electron Beam Irradiation of Polyethylene forSterilization or Cross-Linking

Blocks or rods of UHMWPE were machined into 1 cm thick pieces. Thesesamples were irradiated using a 2.5 MeV van de Graff generator (e-beam)at Massachusetts Institute of Technology by passing under the electronbeam multiple times to achieve the desired radiation dose level(approximately 12.5 kGy per pass).

Example 2 Gamma Irradiation of Polyethylene for Sterilization orCross-Linking

Cylindrical blocks (diameter 89 mm, length larger than 50 cm) were gammairradiated using a Co⁶⁰ source (Steris Isomedix, Northborough, Mass.). Agroup of these blocks were vacuum packaged prior to irradiation andpackaged blocks were irradiated. Another group of blocks were packagedand irradiated under nitrogen.

Example 3 Crystallization of Polyethylene Under High Pressure with PriorMelting (Route I)

Slab-compression molded GUR 1050 was used. Cylinders (5 cm diameter and3 cm high) were machined from these blocks and were covered withaluminum, placed in a metal-laminated thermally-sealable pouch. Vacuumwas pulled inside the pouch and the pouch was sealed. The vacuum-sealedpouched sample was then placed in a pressure chamber. The samples thuspackaged were heated to 180° C. in argon, held at 180° C. for at least 4hours, and then isothermally pressurized to 320 MPa (45,000 psi). Thepressure was held at about constant for 5 hours. At the completion ofthe pressurizing cycle, the samples were cooled to room temperatureunder pressure. Subsequently, the pressure was released.

Example 4 Crystallization of Polyethylene Under High Pressure Below theMelt (Route II)

Slab-compression molded GUR 1050 was used. Cylinders (5 cm diameter and3 cm high) were machined from these blocks and were covered in aluminum,placed in a metal-laminated thermally-sealable pouch. Vacuum was pulledinside the pouch and the pouch was sealed. The vacuum-sealed pouchedsample was then placed in a pressure chamber. The samples thus packagedwere pressurized to 320 MPa (45,000 psi). Then the temperature wasincreased to below the melting temperature of the pressurized UHMWPE(180° C.) at this pressure and held for 5 hours. The samples were cooledto room temperature under a constant pressure and the pressure was thenreleased.

Example 5 Diffusion of Antioxidant into Polyethylene

Slab-compression molded GUR 1050 UHMWPE blocks were machined into thinsections of UHMWPE (thickness=3.2 mm) These samples were placed incontact with CL-tocopherol under 0.5 atm of partial nitrogen vacuum at132° C. for 96 hours. Then, the is samples were taken out, surfacescleaned by wiping off antioxidant, and annealed at 132° C. under 0.5 atmof partial nitrogen/vacuum for 96 hours.

Example 6 Diffusion of Antioxidant into Polyethylene Subsequent toIrradiation (100 kGy)

Slab-compression molded GUR 1050 UHMWPE blocks were gamma irradiated toa dose of 111 kGy in nitrogen. Thin sections of UHMWPE (thickness=3.2mm) were machined and were placed in contact with α-tocopherol under 0.5atm of partial nitrogen vacuum at 136° C. for 96 hours. Then, thesamples were taken out, surfaces cleaned by wiping off antioxidant andannealed at 136° C. under 0.5 atm of partial nitrogen/vacuum for 96hours.

Example 7 Measurement of Antioxidant Diffusion into Polyethylene

To measure the diffusion profile of the antioxidant in the test samplesthat were immersed in α-tocopherol (for example, see Examples 5 and 6),a cross-section was cut out of the immersed section (100-150 μm) usingan LKB Sledge Microtome. The thin cross-section was then analyzed usinga BioRad UMA 500 infrared microscope (Natick, Mass.). Infrared spectrawere collected with an aperture size of 50×50 μm as a function of depthaway from one of the edges that coincided with the free surface of thesample that contacted the antioxidant during immersion. The absorbancebetween 1226 and 1295 cm⁻¹ is characteristic of α-tocopherol andpolyethylene does not absorb near these frequencies. For polyethylene,the 1895 cm⁻¹ wave number for the CH₂ rocking mode is a typical choiceas an internal reference. The normalized value, which is the ratio ofthe integrated absorbances of 1260 cm⁻¹ and 1895 cm⁻¹, is an index thatprovides a relative metric of α-tocopherol composition in polyethylene.FIG. 3 shows the profile of α-tocopherol polyethylene doped by theprocedure described in Example 5 and measured in the manner described inthis example.

Example 8 Measurement of Oxidation Levels in Polyethylene

The oxidation level was quantified as a function of distance away fromfree surfaces on a number of UHMWPE test samples that were subjected tovarious processing steps as described in some of the examples below. Forthis, a thin cross-section (100-150 μm) of the UHMWPE test sample wascut using a LKB Sledge Microtome. A BioRad UMA 500 infrared microscopewas used to measure the extent and depth of oxidation in this section.Infrared spectra were collected with an aperture size of 50×50 μm as afunction of depth away from one of the edges that coincided with thefree surface of the sample. The infrared spectra were analyzed tocalculate an oxidation index, as the ratio of the areas under the 1740cm⁻¹ carbonyl and 1370 cm⁻¹ methylene stretching absorbances.

Example 9 Fatigue Crack Propagation Testing

The fatigue crack propagation was quantified on a number of UHMWPE testsamples that were subjected to various processing steps as described insome of the examples below. For this, fatigue crack propagation testingwas performed on a MiniBionix 858 (MTS, Eden Prairie, Minn.) followingASTM E-647, the standard method for measurement of fatigue crack growthrates. Compact tension (CT) specimens of Type A1 was used, pre-crackedthe notch, and conducted the tests with a stress ratio of 0.1 in a 40°C. water bath to simulate the in vivo environment.

Example 10 Bi-Directional Pin-on-Disk (Pod) Wear Testing

The wear rate was quantified on a number of UHMWPE test samples thatwere subjected to various processing steps as described in some of theexamples below. For this, the wear behavior of the UHMWPE sample wastested using cylindrical shaped samples (9 mm diameter and 13 mm height)on a custom-built bi-directional pin-on-disk (POD) wear tester at afrequency of 2 Hz. Bovine calf serum was used as lubricant andquantified wear gravimetrically at 0.5 million-cycle intervals.Initially, the pins were subjected to 200,000 cycles of POD testing toremove reach a steady state wear rate independent of diffusion orasperities on the surface. Three pins from each group were tested for atotal of 2 million cycles. The wear rate was calculated as the linearregression of wear vs. number of cycles from 0.2 to 2 million cycles.

Example 11 Determination of Crystallinity with Differential ScanningCalorimetry

The crystallinity was quantified on a number of UHMWPE test samples thatwere subjected to various processing steps as described in some of theexamples below. For this, differential scanning calorimetry (DSC) wasused to measure the crystallinity of the polyethylene test samples. TheDSC specimens were weighed with a Sartorius CP 225D balance to aresolution of 0.01 milligrams and placed in an aluminum sample pan. Thepan was crimped with an aluminum cover and placed in a TA instrumentsQ-1000 Differential Scanning Calorimeter. The samples and the referencewere then heated at a heating rate of 10° C./min from −20° C. to 180°C., cooled to −10° C. and subjected to another heating cycle from −20°C. to 180° C. at 10° C./min. Heat flow as a function of time andtemperature was recorded and the cycles are referred to as 1^(st) heat,1^(st) cool and 2^(nd) heat, respectively.

Crystallinity was determined by integrating the enthalpy peak from 20°C. to 160° C., and normalizing it with the enthalpy of melting of 100%crystalline polyethylene, 291 J/g.

Example 12 Crystallinity Measurements of Polyethylene FollowingHigh-Pressure Crystallization by Route I

Compression-molded GUR 1050 UHMWPE (also referred as conventionalpolyethylene) was high pressure-crystallized as described in Example 3.The control samples were compression-molded GUR 1050 UHMWPE withouthigh-pressure crystallization. DSC test samples were prepared from thesetwo types of polyethylenes and were analyzed using a TA InstrumentsQ-1000 calorimeter as described in Example 11.

The high pressure crystallized samples that were tested containedtransparent and opaque sections. When a cross-section was cut out of thecylindrical blocks, the center was most often more transparent than therim. FIG. 4 shows a representative thermogram of the heating cycle ofconventional polyethylene with no high-pressure crystallization historyand a section from the center of high pressure crystallized conventionalpolyethylene. The 1^(st) heat crystallinity of the conventionalpolyethylene was 62% with a peak melting temperature of 134° C. The highpressure crystallized polyethylene showed a 1^(st) heat is crystallinityof 78% with the peak melting temperature at 145° C. and a shoulder at130° C.

The high-pressure crystallization parameters used here resulted in anincrease in the crystallinity of the conventional polyethylene. Inaddition, the shift of the peak melting temperature from 134° C. to 145°C. indicated the formation of larger crystals (extended chain crystals)during high-pressure crystallization.

As discussed above, the high pressure crystallized cylinder ofconventional polyethylene radially exhibited a non-uniform appearance(as shown schematically in FIG. 5). Variations in the crystallinity withthe appearance of the polyethylene are shown in Table 1. A core with adiameter of approximately 2 cm showed high crystallinity. Thecrystallinity decreased towards the rim. At the opaque rim, thecrystallinity was not significantly different from that of conventionalpolyethylene, which may be due to the pressurization medium (argon gas)diffusing into the outer layer of polyethylene and swelling. Theswelling may have resulted in cavitation in polyethylene. Cavitation isknown to scatter light and hence, make the polyethylene appear opaque.

TABLE 1 Crystallinity of conventional polyethylene and high pressurecrystallized (HPC) conventional polyethylene. Material Crystallinity (%)Conventional polyethylene 61.8 ± 1.4 HPC conventional polyethylene,transparent 77.7 ± 1.3 HPC conventional polyethylene, opaque 61.3 ± 2.6

Example 13 Crystallinity Measurements of Previously Irradiated andMelted Polyethylene Following High-Pressure Crystallization by Route I

Compression-molded GUR 1050 was e-beam irradiated to 95 kGy at 120° C.and subsequently melted (WIAM-95). A cylindrical block (diameter 50 mm,length approximately 40 mm) was high pressure crystallized by Route I asdescribed in Example 3.

The WIAM-95 and high-pressure crystallized WIAM-95 were tested using aTA Instruments Q-1000 calorimeter as described in Example 11.

The 1^(st) heat crystallinity was 57% for the WIAM-95 and 62% for thehigh-pressure crystallized WIAM-95. This increase in the crystallinitywas mainly attributed to larger crystals with a peak melting point at141° C. (FIG. 6).

The increase in crystallinity and peak melting temperature withhigh-pressure crystallization was less profound on the irradiated/meltedpolyethylene compared to conventional polyethylene, as described inExample 12. The decrease in the number of high molecular weight linearchains and the reduction in mobility caused by the cross-linkingdecreased the rate of crystal growth. Consequently, during high-pressurecrystallization in the hexagonal phase crystals did not grow to the sameextent in the cross-linked polyethylene as they did in the conventionalpolyethylene.

These results showed that even at the relatively low pressure of 320MPa, it is possible to obtain extended chain crystals for bothconventional (see Example 12) and highly cross-linked polyethylene. Theexperiment showed that high-pressure crystallization of bothconventional (see Example 12) and highly cross-linked polyethylene ledto increases in crystallinity as well as increases in the population oflarger crystals compared to conventional GUR 1050 crystallized atambient pressure.

Example 14 Morphology of Transparent and Opaque Sections on HighPressure Crystallized Samples

Consolidated GUR 1050 (diameter 50 mm, length 90 mm) block was highpressure crystallized by Route I, as described in Example 3.

A thin cross-section of the block showing both transparent and opaqueregions was freeze fractured and gold coated. This cross-section wasanalyzed on a scanning electron microscope under high vacuum using afield emission gun. FIGS. 7A, 7B, and 7C show the morphology of theopaque and transparent regions, and the transitional region,respectively.

The transparent side showed more uniform morphology with fewer grainboundaries and no cavities, whereas the opaque side showed a high numberof grain boundaries and cavities, as seen in FIGS. 7A and 7B. It ispostulated that the cavities are formed by swelling effect of thepressurizing gas (for example, argon gas) used during the high-pressurecrystallization. Cavitation is known to scatter light and hence, makethe polyethylene appear opaque.

Example 15 Determination of Warm Irradiation Temperature

Warm irradiation of polyethylene was performed in order to maintain aspecific crystalline content during irradiation for high cross-linking.Differential scanning calorimetry (DSC) was used to measure thecrystallinity of the polyethylene test samples. The sample and thereference were then heated at a heating rate of 10° C./min from −20° C.to 180° C., cooled to −20° C. at −100° C./min and subjected to anotherheating cycle from −20° C. to 180° C. at 10° C./min. Heat flow as afunction of time and temperature was recorded and the cycles arereferred to as 1^(st) heat, 1^(st) cool and 2^(nd) heat, respectively.

The heat flow was integrated as a function of temperature for the 1^(st)heating cycle of polyethylene from 20° C. to 160° C. The integral ateach temperature was subtracted from the integral at 160° C. and thedifference was divided by the theoretical enthalpy of fusion of a 100%crystalline UHMWPE (291 J/mol). In this way, a plot was obtained wherepercent crystallinity was given as a function of temperature. By usingthis plot, it was possible to determine the temperature where warmirradiation was to be performed with the desired amount of crystallinecontent.

Example 16 High Pressure Crystallized and Irradiated (I-HPC) UHMWPE

GUR 1050 UHMWPE high pressure-crystallized by Route I, as described inExample 3, was machined into 1 cm thick slices (diameter 5 cm) andelectron beam irradiated to a radiation dose of 150 kGy, as described inExample 1, at two different temperatures; room temperature (coldirradiated) (I-HPC1-CI) and at a temperature at which polyethylene wasapproximately 50% crystalline; in this case, 136° C. (warm irradiated)(I-HPC1-WI). The temperature at which the UHMWPE was 50% crystalline wascalculated as described in Example 15.

Example 17 High Pressure Crystallized and Irradiated UHMWPE (I-HPC) withSubsequent High-Pressure Crystallization

UHMWPE prepared as described in Example 16 was further subjected tohigh-pressure crystallization by Route I, as described in Example 3.

The crystallinity values for UHMWPE high pressure-crystallized by RouteI (HPC1), high pressure-crystallized and irradiated (HPC1-CI, HPC1-WI)and high pressure crystallized, cold- or warm-irradiated, andsubsequently high pressure-crystallized by Route I (HPC1-CI-HPC1 orHPC1-WI-HPC1) samples are shown in FIG. 8. Detailed description of theabbreviated processes is shown below in Table 2. Control materials wereunirradiated GUR 1050, 100 kGy cold irradiated GUR 1050, 100-kGy coldirradiated and subsequently melted and 95-kGy warm irradiated andsubsequently melted UHMWPE.

The HPC1 had 1^(st) heat crystallinity of 79%, which decreased to 78%upon cold-irradiation to a dose of 150 kGy (I-HPC1-CI). The HPC1-CI isexpected to contain residual free radicals because of the terminalirradiation step. Therefore, the HPC1-CI was subjected to another stepof HPC1. When the HPC1-CI was heated above the melting point prior topressurization during the second HPC1 step, the residual free radicalswould have recombined. However, following the pressurization andcrystallization, the crystallinity further decreased to 62% in the finalHPC1-CI-HPC1. Nevertheless, the crystallinity of HPC1-CI-HPC1, which hasbeen highly cross-linked and should contain no residual free radicalsdue to the melting during the high-pressure crystallization process, wasstill higher than the crystallinity of both the 100-kGy cold-irradiatedand melted sample and the 95-kGy warm irradiated and melted sample.

TABLE 2 Description of test samples used in high-pressurecrystallization and/or irradiation. Sample ID Description of processHPC1 High pressure crystallized through Route I HPC1-CI High pressurecrystallized through Route I, then e-beam irradiated to 150 kGy at roomtemperature (cold irradiated) HPC1-WI High pressure crystallized throughRoute I, then e-beam irradiated to 150 kGy at 136° C. (warm irradiated)HPC1-CI-HPC1 High pressure crystallized through Route I, then e-beamirradiated to 150 kGy at room temperature (cold irradiated) then highpressure crystallized again through Route I HPC1-WI-HPC1 High pressurecrystallized through Route I, then e-beam irradiated to 150 kGy at 136°C. (warm irradiated), then high pressure crystallized through Route I

Example 18 Cold Irradiation with Subsequent Mechanical Deformation

Two compression molded GUR 1050 rods (diameter 9.1 cm; length 41 cm)were subjected to 100 kGy gamma irradiation in a vacuum package. Bothrods were then heated to 130° C. and one was subsequently deformed underuniaxial compression normal to its long-axis to a compression ratio of2.7 (initial diameter/final diameter). The compression was carried outat 130° C. The compressed rod was held under constant deformation andcooled to room temperature. The load was then released and thedimensions of the rod were recorded (length=58 cm; width=16.6 cm;thickness=40.5 cm). Both the rods were heated to 135° C. to recover theresidual deformation and the final dimensions were recorded(diameter=7.5 cm; length=40 cm). Thus, one rod was subjected tomechanical deformation and thermal processing, while the other was onlysubjected to the identical thermal history without deformation to serveas a control.

Example 19 Free Radical Concentration, Oxidation Levels, and Wear Rateof Irradiated and Mechanically Deformed UHMWPE

Two GUR 1050 blocks, prepared as described in Example 18, were analyzedby using electron spin resonance (ESR) (University of Utah, Departmentof Physics) to quantify the concentration of residual free radicals.Crystallinity was determined by DSC, as described in Example 11. Cubesmachined from both rods were subjected to accelerated aging at 80° C. inair for 5 weeks and the oxidation of the samples was determined by usinginfrared microscopy, as described in Example 8. Finally, the wearbehavior of the mechanically annealed rods (n=3) was determined usingour bi-directional wear tester, using a method as described in Example10.

The ESR analysis showed 2×10¹⁵ spins/gram for the thermal control, whilethe mechanically annealed sample showed no detectable residual freeradicals, identical to 100 kGy irradiated and melted polyethylene. TheDSC analysis showed a crystallinity level of 62±0.5% for the 1^(st) heatof the mechanically annealed sample, comparable to that ofnon-irradiated UHMWPE. The crystallinity level typically decreases to55-57% following post irradiation melting. Accelerated aging led tooxidation in the thermal control (oxidation index=1.30±0.2), which issignificantly more than the mechanically annealed test sample (oxidationindex=0.01±0.01) (p<0.01). The POD wear rate of the mechanicallyannealed rod was found to be 0.8±0.0 mg/million-cycles, which iscomparable to that of 100-kGy irradiated and melted polyethylene.

Example 20 Fatigue Crack Propagation Testing of Unirradiated, Irradiatedand Melted Samples

Compression molded UHMWPE GUR 1050 (γ-sterilized in air to 25 kGy-40kGy), highly cross-linked UHMWPE (γirradiated in vacuum to 100 kGy), and100-kGy highly irradiated and melted polyethylene were used as controlsamples. Gamma irradiation was done as described in Example 2.

Fatigue crack propagation testing was performed as described in Example0.9. The stress intensity factor at crack inception (ΔK_(i)) along withcrystallinity values of control samples are shown in Table 3.Crystallinity was determined by DSC as described in Example 11.Crystallinity of UHMWPE was comparable after low and high doseirradiation. When the high dose irradiated polyethylene was melted,crystallinity decreased significantly (p<0.001). The fatigue strength(ΔK_(i)) decreased by 44% (p<0.0001) when the radiation dose wasincreased from 25-40 kGy to 100 kGy, presumably due to increased numberof cross-links. Melting of the 100-kGy irradiated UHMWPE furtherdecreased the fatigue strength by 19% (p<0.001)), presumably due to thedecrease in crystallinity.

TABLE 3 Stress intensity factor range at crack inception of control andirradiated and melted polyethylenes. Material 25-40-kGy 100-kGy 100-kGyirradiated irradiated irradiated (no melting) (no melting) and meltedSamples tested 3 4 5 ΔK_(i) (MPa · m^(1/2)) 1.29 ± 0.04 0.72 ± 0.04 0.58± 0.03 Crystallinity (%)  62 ± 1.4  64 ± 0.9  57 ± 0.6

Example 21 Fatigue Crack Propagation Testing of High PressureCrystallized UHMWPE

Fatigue crack propagation testing was performed, as described in Example9, on compression-molded unirradiated GUR 1050 UHMWPE that was highpressure-crystallized by Route I as described in Example 3.

The stress intensity factor at crack inception (ΔK_(i)) was 1.37±0.06(n=3) and 1.49 MPa√m (n=2) for GUR 1050 UHMWPE and highpressure-crystallized GUR 1050 UHMWPE, respectively. We machined thecompact tension specimens with crack tip at the core of the highpressure-crystallized cylinder, which, as described in Example 12, wasfound to be the highly crystalline region.

Example 22 Pin-on-Disk (POD) Wear Test of UHMWPE Blended with 0.1% and0.3% Vitamin E Prior to Consolidation

The effects of Vitamin E blended with UHMWPE resin powder prior toirradiation on the wear resistance of irradiated GUR 1050 UHMWPE weredetermined. Vitamin E (α-tocopherol) was mixed with GUR 1050 UHMWPEpowder, in two concentrations, 0.1 wt % and 0.3 wt %, and consolidated.The consolidation of UHMWPE into blocks was achieved by compressionmolding. One additional consolidation was carried out withoutα-tocopherol additive and used as a control. The three consolidatedblocks were machined into halves and one half of each was packaged invacuum and gamma irradiated to 100 kGy, as described in Example 2.

Cylindrical pins, 9 mm in diameter and 13 mm in length, were cut out ofthe irradiated blocks. The pins were first subjected to acceleratedaging at 80° C. for 5 weeks in air and subsequently tested on abi-directional pin-on-disk (POD), as described in Example 10.

The typical wear rate of UHMWPE with no radiation history and noα-tocopherol treatment is around 8.0 milligram per million cycles andfor 100-kGy irradiated and melted UHMWPE is 1 mg/MC. The wear rates forthe 100-kGy irradiated α-tocopherol blended pins were 2.10±0.17 and5.01±0.76 milligram per million cycles for the 0.1% and 0.3 wt %α-tocopherol concentration, respectively. The reduction in wearresistance is less with higher α-tocopherol content.

These results suggest that the cross-link density of UHMWPE, achieved bya high irradiation dose, decreases with increasing concentration ofα-tocopherol content in the mixture. We believe that this is because ofthe antioxidant activity of α-tocopherol acting on the free radicals onUHMWPE chains that would in its absence form cross-links with eachother.

Example 23 Oxidative Stabilization of Irradiated UHMWPE by α-TocopherolDoping

Consolidated GUR 1050 UHMWPE bar stock was gamma irradiated to 65 and100 kGy as described in Example 2. 2 cm cubes were machined of this barstock. The samples were doped with Vitamin E (α-Tocopherol (α-T)) for 16hours at room temperature in air. Following doping, the samples werefurther gamma sterilized at a dose of 27 kGy. These two groups arereferred to as α-T-92 and α-T-127 with a total radiation dose of 92 kGyand 127 kGy, respectively. The control materials was 100-kGy gammairradiated GUR 1050.

All samples were accelerated aged at 80° C. in air for five weeks. Afterthis, the cubes were cut in halves and oxidation levels were assessed asdescribed in Example 8.

The effects of aging on the oxidation of un-doped and α-T doped samplesare shown in FIG. 9. The curves represent splined averages of threesamples. The 100-kGy irradiated control samples showed significantlyhigher oxidation levels when compared to α-T-92 and α-T-127 samples;maximum oxidation indices were 3.74±0.16, 0.48±0.25 (p<0.001), and0.44±0.06 (p<0.001), respectively. It appeared that α-tocopherolprotected irradiated polyethylene against oxidation during acceleratedaging at 80° C. in air.

Example 24 Oxidative Stabilization of High Pressure Crystallized andIrradiated UHMWPE by Vitamin E Doping

Compression-molded GUR 1050 (diameter 0.2″) block was highpressure-crystallized, as described in Example 3. The block was machinedinto thin sections of approximately 8.5 mm thickness. These thinsections were irradiated to a dose of 100-kGy by electron beam, asdescribed in Example 1.

One of the resulting circular sections was cut into four quarters. Onewas doped in α-tocopherol (vitamin E) for 16 hours at room temperaturein air, another was doped in α-tocopherol for 16 hours at 100° C. inair. The two corresponding thermal controls were kept at roomtemperature and at 100° C., respectively, for 16 hours in air withoutdoping. All four samples were cut in halves and one half was acceleratedaged in a convection oven for 5 weeks at 80° C., in air. The other halfwas unaged.

The oxidation profiles for all samples were assessed as described inExample 8. There was significant subsurface oxidation in the agedthermal controls while the α-tocopherol doped samples showedsignificantly lower oxidation levels than controls (p<0.01, and p<0.9001for room temperature (RT) and 100° C. doped samples, see FIGS. 10 and11).

Example 25 Oxidative Stabilization of High Pressure Crystallized andIrradiated UHMWPE by Mechanical Deformation

Compression-molded GUR 1050 (diameter 2″) block is high pressurecrystallized, as described in Example 3. The block is machined into thinsections of approximately 8.5 mm thickness. These thin sections areirradiated to a dose of 100-kGy by electron beam as described in Example1.

One thin section is heated to 137° C. and mechanically deformed underuniaxial compression at this temperature to a compression ratio of about2.5 (initial/final height). The compressed rod is held under constantdeformation and cooled back down to room temperature under constantdeformation. The load is then released and the dimensions of the rodwere recorded. This section is subsequently heated to 144° C. to recoverthe residual deformation. The thin section is cut in halves and one halfwas accelerated aged at 80° C. in air for 5 weeks.

A thin piece (cross-section approximately 3 mm by 3 mm) is machined outof the remaining piece for electron spin resonance (ESR) analysis (atDepartment of Physics, University of Memphis, Tenn.).

The high pressure crystallized and 100-kGy irradiated UHMWPE isstabilized by mechanical deformation and ESR values for this sample arenot expected to be significantly different than the background number ofspins.

Aggressively accelerated aged UHMWPE, which was high pressurecrystallized, 100-kGy irradiated UHMWPE, and stabilized by mechanicaldeformation can show significantly less oxidation than that ofaccelerated aged, high pressure crystallized, and 100-kGy irradiatedcontrol.

Example 26 Pin-on-Disk (POD) Wear Testing of UHMWPE Doped with Vitamin EAfter Irradiation

Consolidated GUR 1050 UHMWPE bar stock was gamma irradiated to 65 and100 kGy. Cylindrical pins (9 mm diameter, 13 mm length) for POD weartesting were machined from these irradiated polyethylenes. The sampleswere doped with vitamin E (α-T) for 16 hours at room temperature in air.Following doping, the samples were further gamma sterilized at a dose of27 kGy. These two groups are referred to as α-T-92 and α-T-127 with atotal radiation dose of 92 and 127 kGy, respectively.

Control samples were 1) 100-kGy gamma irradiated GUR 1050 followed bymelting at 150° C., 2) 105-kGy gamma irradiated GUR 1050 followed byannealing at 120° C. and 3) 25-kGy gamma sterilized GUR 1050 innitrogen. Gamma irradiation was done as described in Example 2.

Half of the cylindrical samples were subjected to accelerated aging at80° C. in air for five weeks. Both unaged and aged samples were thensubjected to POD wear testing, as described in Example 10.

The wear rates of doped and undoped cross-linked and conventionalpolyethylenes before and after accelerated aging are shown in FIG. 12.The wear rate measured for the two groups of α-T-doped, highlycross-linked polyethylene groups are reported along with the wear rateof 25 kGy irradiated conventional polyethylene (γ-sterilized innitrogen), 100 kGy irradiated/melted and 105 kGy irradiated/annealedsamples before or after aging. The wear rate of the 100 kGyirradiated/annealed and conventional polyethylenes increased afteraging. The wear rates of α-T-92 and α-T-127 were equivalent to that ofirradiated and melted UHMWPE. Aging did not change the wear behavior ofeither α-T-92 or α-T-127 (p>0.05). This result indicates that α-T wasable to protect UHMWPE against oxidation and since α-T doped samples didnot oxidize, their wear rate was similar to unaged specimens.

Example 27 The Effect of Extraction by Ethanol on the Oxidation and WearBehavior of Irradiated UHMWPE

Consolidated GUR 1050 UHMWPE bar stock was gamma irradiated to 65 kGyand 100 kGy. Cylindrical pins (9 mm diameter, 13 mm length) for POD weartesting and cubes (2 cm) for accelerated aging and oxidation testingwere machined from these irradiated polyethylenes. The samples weredoped with vitamin E (α-T) for 16 hours at room temperature in air.Following doping, the samples were further gamma sterilized at a dose of27 kGy. These two groups are referred to as α-T-92 and α-T-127 with atotal radiation dose of 92 kGy and 127 kGy, respectively.

Half of the cubes and pins were placed in boiling ethanol overnight toremove α-tocopherol from the UHMWPE. Then, they were placed in aconvection oven for 5 weeks in air at 80° C. for accelerated aging. Theother half were just accelerated aged for 5 weeks at 80° C. in air.

Oxidation profiles for the cubes were assessed as described in Example 8and POD wear testing was done on the pins as described in Example 10.Average maximum oxidation levels observed are as shown in Table 4. Therewas a significant (p<0.05) but small difference between aged andextracted and aged samples for 100-kGy irradiated control and α-T-127(FIG. 13 and Table 4). Therefore, there was no appreciable difference inoxidation behavior between just aged and extracted and aged samples.Extraction in boiling ethanol did not remove the α-tocopherol fromUHMWPE and α-tocopherol was able to protect UHMWPE against oxidation.

Also, the oxidation levels of α-T-92 and α-T-127 were significantlylower than that for the 100-kGy irradiated control for extracted andaged samples. This showed that α-tocopherol was able to protect againstoxidation of irradiated UHMWPE after it was subjected to boiling ethanoltreatment.

TABLE 4 Maximum oxidation values for accelerated aged and ethanolextracted/aged α-tocopherol doped irradiated UHMWPE and 100-kGyirradiated control. Aged Ethanol Extracted and Aged Material Oxidationvalues 100-kGy control 3.74 ± 0.16 4.55 ± 0.33 α-T-92 0.48 ± 0.25 0.62 ±0.14 α-T-127 0.44 ± 0.06 0.60 ± 0.08

Similarly, the wear rates of aged α-T-92 and α-T-127 were not affectedsignificantly by the extraction process (see FIG. 13).

Example 28 The Effect of Cleaning by Washing on the Oxidation and WearBehavior of Irradiated UHMWPE

Slab compression-molded GUR 1050 UHMWPE blocks (Perplas Ltd.,Lancashire, UK) (3″ diameter) were gamma-irradiated in vacuum to a doseof III-kGy (Steris Isomedix, Northborough, Mass.). These blocks werethen machined into half-cubes (2 cm×2 cm×1 cm).

The half-cubes were immersed in α-tocopherol (α-D, L-tocopherol, FischerScientific, Houston, Tex.) at room temperature and 100° C. in air for 1and 16 hours, respectively (n=3 each). Three thermal controls (roomtemperature, 100° C. for 1 and 16 hours) were subjected to the samedoping temperature without α-tocopherol.

Cleaning was performed by a portable Kenmore dishwasher (Sears Inc,Hoffman Estates, Ill.) on normal cycle with rinse and heat drying.During cleaning, all half-cube test samples were placed in a cylindricalnonelastic polyethylene mesh of 2″ diameter and closed at the ends. Thisensured that the samples did not move around, but the cleaning mediumcould get through. Electrasol™ (Reckitt Benckiser Inc., Berkshire, UK)was used as cleaning agent.

Oxidation profiles for the cubes were assessed as described in Example 8and the average of maximum oxidation levels are reported in Table 5.

TABLE 5 Maximum oxidation values for cleaned and accelerated agedcontrol and α-T doped 111-kGy irradiated UHMWPE. RT denotes that dopingwas done at room temperature. Conditions Average Maximum Oxidation Index111-kGy RT control 3.68 ± 0.15 RT 1 hr  038 ± 0.05 RT 16 hrs 0.40 ± 0.03111-kGy 100° C. 1 hr control 0.97 ± 0.04 100° C. 1 hr 0.098 ± 0.003111-kGy 100° C. 16 hrs control 0.70 ± 0.18 100° C. 16 hr 0.080 ± 0.003

These oxidation values for cleaned and aged α-tocopherol-doped 111-kGyirradiated UHMWPE are similar to that of the samples in Example 27 thathad been irradiated to 65 and 100-kGy, α-tocopherol doped, and thengamma sterilized (27-kGy) and aged without cleaning; A. U. 0.48±0.25 and0.44±0.06, respectively (Table 4). The cleaning procedure could not toremove the α-tocopherol already diffused through the surface of theUHMWPE.

Thermal control for 111-kGy irradiated, cleaned and aged samples forUHMWPE diffused with α-tocopherol at 100° C. for 1 hour showed higherlevels of oxidation than that of the α-tocopherol-diffused test samples(p<0.0005). Similarly, thermal control for 111-kGy irradiated, cleanedand aged samples for UHMWPE diffused with α-tocopherol at 100° C. for 16hours showed higher levels of oxidation than that of theα-tocopherol-diffused test samples (p<0.0005). The oxidation levels ofthe controls and test samples did not show significant differencebetween a soak time of 1 hour and 16 hours. The oxidation levels fordoped samples at 100° C. were significantly less than those doped atroom temperature (p<0.01 and p<0.005 for 1 and 16 hours, respectively).The oxidation profile of a representative sample of each preparation isshown in FIG. 14.

Example 29 Calculating Crosslink Density of UHMWPE by Dynamic MechanicalAnalyzer

Crosslink density measurements were performed with a dynamic mechanicalanalyzer (DMA 7e, Perkin Elmer, Wellesley, Mass.). Rectangular pieces ofUHMWPE were set in dental cement and sliced into thin sections (2 mmthick). Small sections were cut out by razor blade from these thinsections to be analyzed (approximately 2 mm by 2 mm). These small pieceswere placed under the quartz probe of the DMA and the initial height ofthe sample was recorded. Then, the probe was immersed in xylene, whichwas subsequently heated to 130° C. and held for 45 minutes. The UHMWPEsamples swelled in boiling xylene until equilibrium was reached (theweight change was less than 0.1%). The final weight was recorded.

The crosslink density was calculated in the following manner:

The ratio of the final height to the initial height was cubed to obtainthe swell ratio, q, assuming homogeneous expansion in all threedirections. Then the crosslink density, υ_(c), was calculated from:

$\upsilon_{c} = {- \frac{{\ln( {1 - q^{- 1}} )} + q^{- 1} + {\chi\; q^{- 2}}}{{\overset{\_}{V}}_{1}q^{{- 1}/3}}}$

where V ₁ is the partial volume of xylene (136 cm³/mol) and χ is theFlory-Huggins interaction parameter defined as χ=0.33+0.55/q. Averagemolecular weight between crosslinks was also calculated.

${\overset{\_}{M}}_{c} = \frac{\rho}{\upsilon_{c}}$

A more densely cross-linked structure will have higher cross-linkingdensity and lower molecular weight between crosslinks than a moreloosely cross-linked structure.

Example 30 Cross-Linking Density of Cold and Warm Irradiated HighPressure Crystallized Polyethylene

The crosslink density and molecular weight between crosslinks wascalculated as described in Example 29 for I-HPC CI and I-HPC WI toinvestigate the differences in cross-linking between these two UHMWPEsdue to the increased amorphous phase in the warm irradiation process(see Table 6).

TABLE 6 Crosslink density and molecular weight between crosslinks forwarm and cold irradiated previously high pressure crystallized UHMWPEs.Molecular Weight Crosslink between Crosslinks Sample Density (mol/m³)(g/mol) I-HPC CI 173 ± 8 (n = 3) 4990 ± 230 (n = 3) opaque I-HPC WI 155± 31 (n = 3) 5711 ± 1042 (n = 3) opaque I-HPC CI 148 ± 36 (n = 3) 6075 ±1670 (n = 3) transparent I-HPC WI 155 ± 13 (n = 2) 5580 ± 487 (n = 2)transparent

Although the warm and cold irradiated I-HPC polyethylenes did not showsignificant differences, these 150-kGy irradiated UHMWPEs showed lowercross-linking ratios than 150-kGy cold-irradiated and melted UHMWPE (209mol/m³; Muratoglu et al., 1999). This is because during irradiation,there was less amorphous phase available in the high pressurecrystallized UHMWPE, as discussed in Example 12 (for example, a 78%crystalline UHMWPE will only have 21% amorphous content available forcross-linking as opposed to about 36% for a 100-kGy cold-irradiatedUHMWPE). The present approach can provide highly crystalline UHMWPE witha markedly higher degree of cross-linking than previous approaches inthe prior art.

Example 31 Vitamin E

Vitamin E (Acros™ 99% D-α-Tocopherol, Fisher Brand), was used in theexperiments described herein, unless otherwise specified. The vitamin Eused is very light yellow in color and is a viscous fluid at roomtemperature. Its melting point is 2-3° C.

Example 32 Plasticization of UHMWPE

Compression-molded GUR 1050 UHMWPE was machined into thin sections(diameter approximately 90 mm, thickness 3.2 mm). One thin section wasplaced in α-tocopherol at 132° C. for 5 hours under partialvacuum/nitrogen. Then, it was taken out of the α-tocopherol, the surfacewas wiped clean with a cotton gauze. The thin section was then placed at132° C. for 48 hours under partial vacuum/nitrogen. α-tocopherol profilein the sample was measured as described in Example 7. The profile wasfound to be uniform with an average α-tocopherol index of 0.92±0.10taken from 16 points along the sample thickness. A thin section ofconsolidated GUR 1050 of the same dimensions was used as control withoutdoping with α-tocopherol.

Dogbone specimens (n=5) were stamped out of this thin section andtesting was done according to ASTM D-638 Standard test method fortensile properties of plastics at a crosshead speed of 10 mm/min. Theengineering strain at break was 521±16% for control UHMWPE and 1107±36%for α-tocopherol-doped and annealed UHMWPE. This result showed thatengineering strain at break was significantly increased when UHMWPE wasdoped uniformly with α-tocopherol. This increase in engineering strainat break may be an indication of the plasticization effect ofα-tocopherol on UHMWPE.

Example 33 Plasticization of Irradiated UHMWPE

A compression-molded GUR 1050 UHMWPE block (3″ diameter, 3′ length) wasirradiated to 100 kGy. Thin sections (thickness 3.2 mm) were machinedfrom the block. One thin section of the block was placed in α-tocopherolat 136° C. for 72 hours under partial vacuum/nitrogen. The thin sectionof the block was taken out of α-tocopherol, the surface was wiped cleanwith a cotton gauze. The thin section was then placed at 136° C. for 100hours under partial vacuum/nitrogen. α-tocopherol profile was measuredas described in Example 7. The profile was found to be uniform (see FIG.15) with an average α-tocopherol index of 3.33±0.22 taken from 16 pointsalong the sample thickness. A thin section of 100 kGy-irradiated GUR1050 UHMWPE was used as control without doping with α-tocopherol.

Dogbone specimens (n≧3) were stamped out of these thin sections andtesting was done according to ASTM D-638 Standard test method fortensile properties of plastics at a crosshead speed of 10 mm/min. Theelongation-to-break (EAB), ultimate tensile stress (UTS) and yieldstrength (YS) of 100 kGy-irradiated and 100 kGy-irradiated andα-tocopherol doped UHMWPE are shown in Table 7.

TABLE 7 Mechanical properties of 100 kGy irradiated and 100 kGyirradiated and α-tocopherol doped UHMWPE. Average Vitamin E Material UTS(MPa) YS (MPa) EAB (%) Index 100-kGy 33 ± 1 21 ± 2 214 ± 7 —α-Tocopherol 40 ± 3 21 ± 2 241 ± 6 3.33 ± 0.22 doped 100-kGy

The engineering strain at break was 741±46% for 100 kGy irradiatedUHMWPE and 1049±135% for α-tocopherol-doped, irradiated UHMWPE. Theseresults showed that UTS, EAB and engineering strain at break weresignificantly increased when irradiated UHMWPE was doped withα-tocopherol. These increases are indications of the plasticizationeffect of α-tocopherol on irradiated UHMWPE.

Example 34 High Pressure Crystallization of UHMWPE Blended with VitaminE Prior to Consolidation

The effects of vitamin E on the mechanical properties of high pressurecrystallized UHMWPE were determined. Vitamin E (α-tocopherol) was mixedwith GUR 1050 UHMWPE powder at a concentration of 0.1 wt % andconsolidated. The consolidation of UHMWPE into blocks was achieved bycompression molding.

A block of approximately 2″ in diameter and 2″ in height was highpressure crystallized through Route I, as described in Example 3.

Thin sections (thickness=3.2 mm) were machined from high pressurecrystallized, vitamin E-blended UHMWPE.

First heat crystallinity of blended UHMWPE and high pressurecrystallized, blended UHMWPE was determined as described in Example 11.

Dogbone specimens (n≧2) were stamped out of these thin sections andtesting was done according to ASTM D-638 Standard test method fortensile properties of plastics at a crosshead speed of 10 mm/min. Theelongation-to-break (EAB), ultimate tensile stress (UTS) and yieldstrength (YS) of blended UHMWPE and high pressure crystallized, blendedUHMWPE are shown in Table 8.

TABLE 8 The elongation-to-break, ultimate tensile stress, and yieldstrength of blended UHMWPE. Crystal- linity (%) UTS (MPa) YS (MPa) EAB(%) 0.1 wt % blended 64 ± 0.5 55 ± 3 23 ± 1 423 ± 8 UHMWPE HPC 0.1 wt %77 ± 1 63 ± 4 26 ± 3 576 blended UHMWPE HPC UHMWPE 77 ± 2 56 ± 6 24 ± 2361 ± 31

0.1 wt % blended UHMWPE showed an increase in UTS, YS and EAB comparedto high pressure crystallized virgin UHMWPE and 0.1 wt % blended UHMWPEprior to high pressure crystallization. The deformed sections of thedog-bone samples of the high pressure crystallized 0.1 wt % blendedUHMWPE showed extensive whitening, which is an indication of cavitationin these samples.

Example 35 Irradiation of UHMWPE Blended with Vitamin E Prior toConsolidation

The effects of vitamin E on the mechanical and wear properties ofirradiated UHMWPE were determined. Vitamin E (α-tocopherol) was mixedwith GUR 1050 UHMWPE powder at a concentration of 0.1 wt % andconsolidated. The consolidation of UHMWPE into blocks was achieved bycompression molding.

A 5 cm×10 cm×10 cm blended block was irradiated by gamma irradiation toa dose of 150 kGy. Thin sections (thickness=3.2 mm) and cylindrical pins(diameter 9 mm, height 13 mm) were machined from the irradiated block.

The crystallinity of blended and irradiated UHMWPE was determined asdescribed in Example 11.

The cross-linking density of blended and irradiated UHMWPE wasdetermined as described in Example 29.

Dogbone specimens (n≧2) were stamped out of these thin sections andtesting was done according to ASTM D-638 Standard test method fortensile properties of plastics at a crosshead speed of 10 mm/min.

The pin-on-disc (POD) wear rate of blended and irradiated UHMWPE wasquantified using POD testing as described in Example 10.

The crystallinity of 0.1 wt % α-tocopherol blended and 150 kGyirradiated UHMWPE was 65±4%. The cross-linking density, as measured bydynamic mechanical analyzer, was 166±2 mol/m³. The ultimate tensilestrength was 40±3 MPa, the yield strength was 20±1 MPa, and theelongation-at-break was 244±22%. The POD wear rate was 1.9±0.3mg/million-cycles. In comparison, a 150 kGy electron beam irradiatedUHMWPE showed a ultimate tensile strength (UTS) of 29±1 MPa, a yieldstrength (YS) of 22±1 MPa and an elongation-at-break (EAB) of 219±16%.

Example 36 High Pressure Crystallization of Irradiated UHMWPE Blendedwith Vitamin E Prior to Consolidation

The effects of vitamin E on the mechanical properties of high pressurecrystallized, irradiated UHMWPE. Vitamin E (α-tocopherol) was mixed withGUR 1050 UHMWPE powder at a concentration of 0.1 wt % and consolidatedwere determined. The consolidation of UHMWPE into blocks was achieved bycompression molding.

A 5 cm×10 cm×10 cm blended block was irradiated by gamma irradiation toa dose of 150 kGy.

A block of approximately 2″ in diameter and 2″ in height was machinedfrom the above-described block and placed in a pressure chamber inwater. The samples were heated to 185° C. for 5 hours, and thenisothermally pressurized to 45,000 psi. The pressure and temperature washeld constant for 5 hours. At the completion of the pressurizing cycle,the samples were cooled to room temperature under pressure.Subsequently, the pressure was released.

The crystallinity of blended and irradiated UHMWPE was determined asdescribed in Example 11.

Thin sections (thickness=3.2 mm) were machined from this high pressurecrystallized, irradiated block. Dogbone specimens (n≧9) were stamped outof these thin sections and testing was done according to ASTM D-638Standard test method for tensile properties of plastics at a crossheadspeed of 10 mm/min.

The crystallinity of high pressure crystallized, 150-kGy irradiated, 0.1wt % α-tocopherol blended UHMWPE was 70±1%. The ultimate tensilestrength of high pressure crystallized, 150-kGy irradiated, 0.1 wt %α-tocopherol blended UHMWPE was 37±2 MPa, the yield strength was 23±1mPa and the elongation-at-break was 234±0%.

Example 37 Cross-Link Density of α-Tocopherol Blended and IrradiatedUHMWPE

The effects of vitamin E on the cross-linking efficiency of irradiatedUHMWPE, were determined. Vitamin E (α-tocopherol) was mixed with GUR1050 UHMWPE powder at a concentration of 0.1, 0.3 and 1.0 wt % andconsolidated. The consolidation of UHMWPE into blocks (5×10×10 cm) wasachieved by compression molding. Virgin UHMWPE was used as control.

One block of each was irradiated by gamma irradiation to 65, 100, 150and 200 kGy.

Thin sections (thickness=3.2 mm) were machined from the α-tocopherolblended and irradiated UHMWPEs.

Cross-link density of α-tocopherol-blended, irradiated UHMWPE wasdetermined as described in Example 29.

TABLE 9 Cross-link density (mol/m³) of α-tocopherol blended andsubsequently irradiated UHMWPEs. α-Tocoph- erol Concen- Radiation Dosetration 65 kGy 100 kGy 150 kGy 200 kGy Virgin 132 ± 25 175 ± 19 203 ± 14220 ± 5  0.1 wt % 119 ± 3  146 ± 4  166 ± 2  212 ± 13 0.3 wt % 71 ± 2 93± 4 146 ± 5  144 ± 4  1.0 wt % 61 ± 5 73 ± 4 75 ± 3 89 ± 6

The results showed that increased α-tocopherol concentration in UHMWPEprior to irradiation decreased the cross-linking of irradiated UHMWPE(see Table 9).

Example 38 High Pressure Crystallized, Irradiated, and SubsequentlyMelted UHMWPE

A block of approximately 2″ in diameter and 2″ in height was machinedfrom GUR 1050 ram extruded stock and placed in a pressure chamber inwater. The block was heated to 185° C. for 5 hours, and thenisothermally pressurized to 45,000 psi. The pressure and temperature washeld constant for 5 hours. At the completion of the pressurizing cycle,the samples were cooled to room temperature under pressure.Subsequently, the pressure was released.

A 1 cm-thick circular piece was machined from the high pressurecrystallized UHMWPE. This piece was irradiated to 150 kGy by usingelectron beam irradiation in air as described in Example 1. Thinsections (3.2 mm) were machined from this piece and one of these thinsections was melted in vacuum at 170° C. It was kept two hours in themelt and cooled down to room temperature under vacuum.

The crystallinity of high pressure crystallized, irradiated and meltedUHMWPE was determined as described in Example 11, and the tensileproperties were determined by mechanical testing according to ASTMD-638.

The crystallinity of high pressure crystallized, 150-kGy irradiated andmelted UHMWPE was 59±1%, the ultimate tensile strength was 36±0 MPa andthe elongation at break was 223±26%.

Example 39 High Pressure Crystallized, Irradiated and Subsequently HighPressure Crystallized UHMWPE

A block of approximately 2″ in diameter and 3″ in height is machinedfrom GUR 1050 ram extruded stock and placed in a pressure chamber inwater. The block is heated to 185° C. for 5 hours, and then isothermallypressurized to 45,000 psi. The pressure and temperature are heldconstant for 5 hours. At the completion of the pressurizing cycle, thesamples are cooled to room temperature under pressure. Subsequently, thepressure is released.

A 1 cm-thick circular piece is machined from the high pressurecrystallized UHMWPE. The piece is irradiated to 150 kGy by usingelectron beam irradiation in air as described in Example 1.

The irradiated piece is placed in a pressure chamber in water. The blockis heated to 195° C. for 5 hours, and then isothermally pressurized to55,000 psi. The pressure and temperature are held constant for 5 hours.At the completion of the pressurizing cycle, the samples are cooled toroom temperature under pressure. Subsequently, the pressure is released.

Example 40 Cycles of High Pressure Crystallization and SubsequentIrradiation on UHMWPE

A block of approximately 2″ in diameter and 3″ in height is machinedfrom GUR 1050 ram extruded stock and placed in a pressure chamber inwater. The block is heated to 185° C. for 5 hours, and then isothermallypressurized to 45,000 psi. The pressure and temperature are heldconstant for 5 hours. At the completion of the pressurizing cycle, thesamples are cooled to room temperature under pressure. Subsequently, thepressure is released.

A 1 cm-thick circular piece is machined from the high pressurecrystallized UHMWPE. The piece is irradiated to 50 kGy by using electronbeam irradiation in air as described in Example 1.

The 50 kGy irradiated piece is placed in a pressure chamber in water.The block is heated to 190° C. for 5 hours, and then isothermallypressurized to 50,000 psi. The pressure and temperature are heldconstant for 5 hours. At the completion of the pressurizing cycle, thesamples are cooled to room temperature under pressure. Subsequently, thepressure is released.

This piece is irradiated to 50 kGy by using electron beam irradiation inair as described in Example 1 for a cumulative irradiation dose of 100kGy.

This 100-kGy irradiated piece is placed in a pressure chamber in water.The block is heated to 190° C. for 5 hours, and then isothermallypressurized to 55,000 psi. The pressure and temperature are heldconstant for 5 hours. At the completion of the pressurizing cycle, thesamples are cooled to room temperature under pressure. Subsequently, thepressure is released.

This piece is irradiated to 50 kGy by using electron beam irradiation inair as described in Example 1 for a cumulative irradiation dose of 150kGy.

This 150-kGy irradiated piece is placed in a pressure chamber in water.The block is heated to 195° C. for 5 hours, and then isothermallypressurized to 60,000 psi. The pressure and temperature are heldconstant for 5 hours. At the completion of the pressurizing cycle, thesamples are cooled to room temperature under pressure. Subsequently, thepressure is released.

The cross-link density, crystallinity and mechanical properties aredetermined after each irradiation and crystallization step.

Example 41 High Pressure Crystallization of Highly-Crosslinked UHMWPE

A block of approximately 2″ in diameter and 3″ in height was machinedfrom GUR 1050 UHMWPE stock that has been compression molded, electronbeam irradiated at 120° C. to 65 kGy and subsequently melted. The blockwas placed in a pressure chamber in water. The block was heated to 195°C. for 5 hours, and then isothermally pressurized to 52,000 psi. Thepressure and temperature were held constant for 5 hours. At thecompletion of the pressurizing cycle, the sample was cooled to roomtemperature under pressure. Subsequently, the pressure was released.

Thin sections (3.2 mm thick) were machined from this high pressurecrystallized highly cross-linked and melted UHMWPE. Mechanical testingwas done on dog-bone shaped specimens in accordance with ASTM D-638.Crystallinity was measured as described in Example 11. The crystallinitywas 63±1%, the ultimate tensile strength was 42±4 MPa and the elongationat break was 354±20%. Before high pressure crystallization, thecrystallinity was 59±0% and the ultimate tensile strength was 35±2 MPa.

Example 42 High Pressure Crystallization of a Highly-Crosslinked MedicalDevice

A highly cross-linked medical device, such as a tibial knee insert oracetabular liner, machined from a ram extruded or thermally annealed GUR1050 UHMWPE stock is placed in a pressure chamber in water. The liner isheated to 195° C. for 5 hours and then isothermally pressurized to60,000 psi. The pressure and temperature are held constant for 5 hours.At the completion of the pressurizing cycle, the sample is cooled toroom temperature under pressure. Subsequently, the pressure is released.

Example 43 High Pressure Crystallization of Irradiated and Doped UHMWPEby Heating Before Pressurizing (Route I)

A medical device, such as tibial knee insert or acetabular liner, ismachined out of UHMWPE stock material. The device is irradiated to 65 or100 kGy with electron beam or gamma irradiation in an inert environment.Subsequently, the device is doped with α-tocopherol. The device is thenplaced in a pressure chamber in water. The device is heated to 195° C.for 5 hours, and then isothermally pressurized to at least 45,000 psi,preferably 55,000 psi. The pressure and temperature are held constantfor 5 hours. At the completion of the pressurizing cycle, the sample iscooled to room temperature under pressure. Subsequently, the pressure isreleased.

Example 44 High Pressure Crystallization of Irradiated and Doped UHMWPEby Pressurizing Before Heating (Route II)

A medical device, such as tibial knee insert or acetabular liner, ismachined out of UHMWPE stock material. The device is irradiated to 65 or100 kGy with electron beam or gamma irradiation in an inert environment.Subsequently, the device is doped with α-tocopherol. The device is thenplaced in a pressure chamber in water. The device is first pressurizedto at least 45,000 psi, preferably 55,000 psi and subsequently heated to195° C. for 5 hours. The pressure and temperature are held constant for5 hours. At the completion of the pressurizing cycle, the sample iscooled to room temperature under pressure. Subsequently, the pressure isreleased.

Example 45 High Pressure Crystallization of Irradiated UHMWPE ContainingResidual Free Radicals by Pressurizing Before Heating (Route II)

UHMWPE stock is annealed to reduce thermal stresses locked-in during theconsolidation of the UHMWPE powder. The annealing is carried out asfollows: heat to 130° C. and hold for 5 hour; cool down to 125° C. at 1°C./hour and hold for 5 hours; cool down to 120° C. at 1° C./hour andhold for 5 hours; cool down to 115° C. at 1° C./hour and hold for 5hours; cool down to 110° C. at 1° C./hour and hold for 5 hours; cooldown to 105° C. at 1° C./hour and hold for 5 hours; cool down to 100° C.at 1° C./hour and hold for 5 hours; and cool down to room temperature at1° C./hour.

A medical device, such as tibial knee insert or acetabular liner, ismachined out of the annealed UHMWPE stock material. The device isirradiated to 65 or 100 kGy with electron beam or gamma irradiation inan inert environment. The device contains residual free radicals at thisstage. Subsequently, the device is placed in a pressure chamber inwater. The device is first pressurized to at least 45,000 psi,preferably to 55,000 psi, and subsequently heated to at least 180° C. orpreferably to 195° C. for 5 hours. The pressure and temperature are heldconstant for at least 5 hours. At the completion of the pressurizingcycle, the sample is cooled to room temperature under pressure.Subsequently, the pressure is released. At the completion of the highpressure crystallization the device is expected to have no detectableresidual free radicals and high crystallinity.

Example 46 High Pressure Crystallization of Irradiated UHMWPE ContainingResidual Free Radicals by Heating Before Pressurizing (Route I)

UHMWPE stock is annealed to reduce thermal stresses locked-in during theconsolidation of the UHMWPE powder. The annealing is carried out asfollows: heat to 130° C. and hold for 5 hour; cool down to 125° C. at 1°C./hour and hold for 5 hours; cool down to 120° C. at 1° C./hour andhold for 5 hours; cool down to 115° C. at 1° C./hour and hold for 5hours; cool down to 110° C. at 1° C./hour and hold for 5 hours; cooldown to 105° C. at 1° C./hour and hold for 5 hours; cool down to 100° C.at 1° C./hour and hold for 5 hours; and cool down to room temperature at1° C./hour.

A medical device, such as tibial knee insert or acetabular liner, ismachined out of the annealed UHMWPE stock material. The device isirradiated to 65 or 100 kGy with electron beam or gamma irradiation inan inert environment. The device contains residual free radicals at thisstage. Subsequently, the device is placed in a pressure chamber inwater. The device is first heated to at least 180° C. or preferably to195° C. for 5 hours, and subsequently pressurized to at least 45,000psi, preferably to 55,000 psi. The pressure and temperature are heldconstant for at least 5 hours. At the completion of the pressurizingcycle, the sample is cooled to room temperature under pressure.Subsequently, the pressure is released. At the completion of the highpressure crystallization the device is expected to have no detectableresidual free radicals and high crystallinity.

It is to be understood that the description, specific examples and data,while indicating exemplary embodiments, are given by way of illustrationand are not intended to limit the present invention. Various changes andmodifications within the present invention will become apparent to theskilled artisan from the discussion, disclosure and data containedherein, and thus are considered part of the invention.

The invention claimed is:
 1. A method of making an oxidation resistant,cross-linked polymeric blend comprising: a) mixing a polymeric materialwith one or more additives to form a polymeric blend in the absence of asupercritical fluid; b) consolidating the polymeric blend; c)irradiating the polymeric blend by ionizing radiation, thereby forming across-linked polymeric blend; d) mechanically deforming the cross-linkedpolymeric blend below its melting point, thereby forming a mechanicallydeformed cross-linked polymeric blend; and e) annealing the mechanicallydeformed cross-linked polymeric blend at a temperature that is above orbelow the melting point, thereby forming an oxidation resistantcross-linked polymeric blend.
 2. The method of claim 1, wherein thepolymeric material is a polyolefin, a polypropylene, a polyamide, apolyether ketone, or a mixture thereof.
 3. The method of claim 2,wherein polyolefin is selected from a group consisting of a low-densitypolyethylene, high-density polyethylene, linear low-densitypolyethylene, ultra-high molecular weight polyethylene (UHMWPE), or amixture thereof.
 4. The method of claim 1, wherein the polymericmaterial is polymeric resin powder, polymeric flakes, polymericparticles, or a mixture thereof or an additive.
 5. The method of claim1, wherein the radiation dose is between about 25 and about 1000 kGy. 6.The method of claim 1, wherein the radiation dose is about 65 kGy, about75 kGy, about 150 kGy or about 200 kGy.
 7. The method of claim 1,wherein the radiation is a gamma irradiation.
 8. The method of claim 1,wherein the radiation is an electron beam irradiation.
 9. The method ofclaim 1 further comprising: a) doping the cross-linked polymeric blendwith an antioxidant by diffusion in the absence of a supercriticalfluid, thereby forming an antioxidant-doped cross-linked polymericblend; and b) annealing the antioxidant-doped, cross-linked polymericblend at a temperature below the melting point of the antioxidant-doped,cross-linked polymeric blend, thereby forming a cross-linked, oxidationresistant and homogenized polymeric blend.
 10. The method of claim 1further comprising: a) machining the oxidation resistant cross-linkedpolymeric blend, thereby forming an oxidation resistant cross-linkedmedical implant; b) doping the oxidation resistant cross-linked medicalimplant with an additive by diffusion in the absence of a supercriticalfluid, thereby forming an additive-doped oxidation resistantcross-linked medical implant; and c) annealing the additive-dopedpolymeric blend at a temperature below the melting point of theadditive-doped polymeric blend, thereby forming a medical implantcomprising an additive-doped and homogenized polymeric blend.
 11. Themethod of claim 1, wherein the polymeric material is irradiated at atemperature between about room temperature and about the peak meltingtemperature of the polymeric blend.
 12. The method of claim 1, whereinthe polymeric blend is irradiated at a temperature above the peakmelting point of the polymeric blend.
 13. The method of claim 1, whereinat least one additive is an antioxidant.
 14. A method of claim 1,wherein at least one additive is vitamin E.
 15. The method in claim 1,wherein the additive concentration is about 0.01 wt/wt %, 0.02 wt/wt %,0.05 wt/wt %, 0.1 wt/wt %, 0.2 wt/wt %, 0.5 wt/wt %, or 1.0 wt/wt %. 16.The method according to claim 1, wherein the polymeric blend containsmore than one antioxidant.
 17. The method of claim 1, wherein thecross-linked polymeric blend is mechanically deformed at a temperaturebelow the melting point of the cross-linked polymeric blend.
 18. Themethod of claim 1, wherein the annealing is carried out in air for atleast for one minute to about 5 hours or more at about 130° C.
 19. Themethod of claim 1, wherein the cross-linked polymeric blend ismechanically deformed uniaxially.
 20. The method of claim 1, wherein thecross-linked polymeric blend is mechanically deformed to a compressionratio of about 2.5 at about 130° C.
 21. The method of claim 1, whereinthe cross-linked polymeric blend is heated to a temperature betweenabove the room temperature and below the melt, and then mechanicallydeformed.
 22. The method of claim 1, wherein the cross-linked polymericblend is heated to a temperature of about 130° C., and then mechanicallydeformed.
 23. The method of claim 1, wherein the polymeric blend iscompression molded to a second material, and wherein the second materialis a porous material.
 24. The method of claim 1, wherein the polymericblend is compression molded to a second material, and wherein the secondmaterial is metallic.
 25. A method of making an oxidation resistantcross-linked blend of polymeric material comprising: a) blending thepolymeric material with one or more additives in the absence of asupercritical fluid; b) consolidating the blend; and c) irradiating theblend of polymeric material with ionizing radiation at an elevatedtemperature that is above room temperature and below the melting pointof the blend of polymeric material, thereby forming a cross-linked blendof polymeric material.
 26. The method of claim 25, wherein at least oneof the additives is an antioxidant.
 27. The method of claim 25, whereinthe polymeric material is a polyolefin, a polypropylene, a polyamide, apolyether ketone, or a mixture thereof.
 28. The method of claim 27,wherein polyolefin is selected from a group consisting of a low-densitypolyethylene, high-density polyethylene, linear low-densitypolyethylene, ultra-high molecular weight polyethylene (UHMWPE), or amixture thereof.
 29. The method of claim 25, wherein the polymericmaterial is irradiated at a temperature between about room temperatureand less than about 155° C.
 30. The method of claim 25, wherein theblend of polymeric material is irradiated at a temperature of about 90°C.
 31. The method of claim 25, wherein the blend of polymeric materialis irradiated at a temperature of about 100° C.
 32. The method of claim25, wherein the blend of polymeric material is irradiated at atemperature of about 110° C.
 33. The method of claim 25, wherein theblend of polymeric material is irradiated at a temperature of about 120°C.
 34. The method of claim 25, wherein the blend of polymeric materialis irradiated at a temperature of about 130° C.
 35. The method of claim25, wherein the blend of polymeric material is irradiated at atemperature of about 135° C.
 36. The method of claim 25, wherein theirradiation dose is more than 1 kGy to 100 kGy, or more.
 37. A method ofmaking oxidation resistant cross-linked and interlocked hybrid materialcomprising: a) blending the polymeric material with one or moreadditives, thereby forming a polymeric blend in the absence of asupercritical fluid; b) compression molding the polymeric blend to thecounterface of a second material, thereby forming an interlocked hybridmaterial having an interface between the polymeric blend and the secondmaterial; and c) irradiating the interlocked hybrid material withionizing radiation at an elevated temperature that is above roomtemperature and below the melting point of the polymeric blend, therebyforming a cross-linked and interlocked hybrid material.
 38. The methodof claim 37, wherein the second material is a metallic mesh or back, anon-metallic mesh or back, a tibial tray, a patella tray, or anacetabular shell.
 39. The method of claim 37, wherein the polymericmaterial is a polyolefin, a polypropylene, a polyamide, a polyetherketone, or a mixture thereof.
 40. The method of claim 39, whereinpolyolefin is selected from a group consisting of a low-densitypolyethylene, high-density polyethylene, linear low-densitypolyethylene, ultra-high molecular weight polyethylene (UHMWPE), or amixture thereof.
 41. The method of claim 37, wherein the interlockedhybrid material is irradiated at a temperature between about roomtemperature and less than about 155° C.
 42. The method of claim 37,wherein the interlocked hybrid material is irradiated at a temperatureof about 90° C.
 43. The method of claim 37, wherein the interlockedhybrid material is irradiated at a temperature of about 100° C.
 44. Themethod of claim 37, wherein the interlocked hybrid material isirradiated at a temperature of about 110° C.
 45. The method of claim 37,wherein the interlocked hybrid material is irradiated at a temperatureof about 120° C.
 46. The method of claim 37, wherein the interlockedhybrid material is irradiated at a temperature of about 130° C.
 47. Themethod of claim 37, wherein the interlocked hybrid material isirradiated at a temperature of about 135° C.
 48. The method of claim 37,wherein the irradiation dose is more than 1 kGy to 100 kGy, or more. 49.The method of claim 37, wherein the second material is a porous.
 50. Themethod of claim 37, wherein the second material is metallic.